透脓散抗肿瘤作用及其机制的研究
摘要
目的：探讨透脓散提取液抗肿瘤作用及其可能的机制。
方法：应用液相色谱-质谱联用技术测定透脓散总提物成分；MTT法检测不同浓度透脓散提物对不同肿瘤细胞(人淋巴瘤Raji细胞,人肠癌LOVO细胞)的增殖抑制率；流式细胞术检测透脓散提液对Raji细胞和LOVO细胞凋亡率及细胞周期的影响；RT-PCR检测透脓散提取液对Raji细胞和LOVO细胞PI3K/AKT信号通路相关分子(PI3K,Akt,m-TOR, p70S6K1,Bad,NF-KB,caspase9,caspase3)的mRNA的表达；Westernblot法检测透脓散提取液对Raji细胞和LOVO细胞PI3K/AKT信号通路相关分子(PI3K,p-Akt,p-mTOR,p-p70S6K1, p-Bad,NF-KB,caspase9,caspase3)蛋白表达的变化；急性毒性实验检测透脓散用药的安全性；根据荷肠癌LOVO细胞裸鼠移植瘤的体积和移植瘤重量计算透脓散提取液的抑瘤率；HE染色光镜观察肿瘤组织的形态结构。免疫组织化学法检测透脓散提取液对肿瘤组织P13K/AKT信号通路相关分子蛋白的表达：ELISA检测裸鼠血清Th1/Th2型细胞因子的含量。
结果：1透脓散提取液主要的化学成分为：毛蕊异黄酮葡萄糖苷,芒柄花苷洋,川芎内酯Ⅰ,毛蕊异黄酮,芒柄花黄素,黄芪甲苷,藁本内酯,且醇提液的成分明显高于水提液。2透脓散提取液可抑制Raji细胞和LOVO细胞的增殖活性并具有明显剂量和时间依赖性。对Raji细胞的72小时半数抑制率为(Half maximal inhibitory concentration,IC50)817.142μg/mL,对LOVO细胞的48小时IC50为：347.603μg/mL (258.526μg/mL to471.545μg/mL)。3透脓散提取液可诱导Raji细胞,LOVO细胞凋亡并阻滞细胞周期在G1期。125μg/mL,250μg/mL和500μg/mL透脓散提取液干预Raji细胞,48h后细胞的凋亡率分别为：12.23±1.98%(P<0.05),20.97+3.96%(P<0.01)和30.4±4.87%(P<0.01),与空白对照组6.02±1.01%相比具有显著的统计学意义。G1期的比例逐渐增高,分别为：44.80%±2.36%(P<0.05),55.48%+2.71%(P<0.01),66.76%±2.25%(P<0.01)与对照组39.66%±2.01%相比具有统计学意义。应用62.5μg/mL,125μg/mL,250μg/mL透脓散醇提液干预LOVO细胞48h后,LOVO细胞的凋亡率分别为：12.8%±1.58%(P<0.05),19.9%±2.16%,(P<0.01),29.57±2.76%(P<0.01)与对照组(7.3%±1.06%)相比具有显著的统计学意义。G1期细胞的比例逐渐增多,分别为：45.45%±2.54%(P<0.05),56.13%±2.54%(P<0.01),66.05%+2.54%(P<0.01)与对照组40.02%＋0.69%相比具有统计学意义。250μg/mL透脓散提取物干预Raji细胞48小时后明显降低Raji细胞NF-κB mRNA及蛋白的表达,增加Bad, caspase-9, caspase-3mRNA及蛋白的表达且具有明显的剂量依赖性。125μg/mL透脓散醇提液干预LOVO细胞48小时后明显降低PI3K, AKT, mTOR, p70s6kl mRNA表达,而Caspase-9,Caspase-3mRNA表达明显增加,PI3K, p-AKT, p-mTOR, p-p70s6kl蛋白表达降低,而Caspase-9, Caspase-3蛋白表达增加,同样具有明显的剂量依赖性。
透脓散提取液最大给药量40000mg/kg时对裸鼠未见明显毒性。高、中、低剂量组的透脓散提取液抑瘤率分别为：67.11%、48.68%、36.84%。免疫组化显示透脓散组P13K,p-Akt, p-mTOR, p-P70S6K1, VEGF, CD31蛋白表达降低,caspase-9, caspase-3蛋白表达增加,且随着剂量的增高,作用逐渐增强。此外,透脓散能调节移植瘤裸鼠的免疫功能,上调Thl型细胞因子(IL-2,IL-12),下调Th2型细胞因子(IL-6,IL-10),从而纠正移植瘤裸鼠机体Thl/Th2漂移,且此效应具有明显的剂量依赖性。
结论：1透脓散提取液可从基因转录和蛋白表达两个层面调控PI3K/AKT信号转导通路中多个分子的表达,从而发挥其抑制Raji细胞、LOVO细胞的增殖,诱导细胞凋亡,阻滞细胞停滞在G1期的作用。
2透脓散提取液可能通过调控PI3K/AKT信号转导通路中多个分子的表达、纠正移植瘤裸鼠的Th1/Th2漂移从而发挥抑制LOVO裸鼠移植瘤的生长的作用。
3透脓散可作为一种有潜力治疗恶性肿瘤的经典方剂。
AIM:To investigate the anti-cancer effects of Tou Nong San extracts (TNSEs) and its possible mechanism.
METHODS:LC-MS Assay for TNS extract. The cytotoxic effect of TNSE on Raji cells and LOVO cells was measured by3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and apoptosis were determined by flow cytometry(FCM).The molecular mechanisms of TNSE-mediated apoptosis were further investigated by reverse transcription-polymerase chain reaction (RT-PCR) analysis of the mRNA expression of nuclear factor-KB (NF-κB), Bcl-xL and Bcl-2-associated death promoter (Bad), caspase-9and caspase-3,PI3K, Akt, mTOR, p70s6k1, and by Western blotting to detect the proteins expression of NF-κB, Bad,PI3K,p-Akt, p-mTOR, p-p70s6k1, caspase-9, caspase-3.The safty of TNSEs was detected by acute toxicity testing.The inhibition ratio was gained on the base of the weight and volume of transplanted tumor, morphosis of tumor was detected by hematoxylin and eosin (HE)stain, the proteins expression of PI3K,p-Akt,p-mTOR,p-p70s6k1, caspase-9, caspase-3,VEGF,CD31were detect by immuno-histochemical(IHC) method and the content of cytokine of Thl/Th2was tested by Enzyme-Linked Immunosorbent Assay(ELISA).
RESULTS:The contents of7major components in TNSEs were Calycosin-7-O-b-D-glucoside, Formononetin-7-O-b-D-glucoside senkyunolide I, Calycosin,formononetin, Astragaloside IV, Z-Ligustilide.TNSEs inhibited Raji cells and LOVO cells proliferation in dose-and time-dependent manners. The Half maximal inhibitory concentration(IC50) of Raji cells was817.142μg/mL at72h,and that of LOVO cells was347.603μg/mL at48h. The apoptosis and Glaresst of these two cell lines were found after treated with TNSEs. After48h treatment with various concentrations of TNSEs (125,250and500μg/mL), the apoptosis rates of Raji cells were12.23±1.98%(P<0.05),20.97±3.96%(P<0.01) and30.4±4.87%(P<0.01), respectively, compared with that of the control (6.02±1.01%).and the G1arrest was also found that was The proportion of G1cells was44.80%±2.36%(P<0.05),55.48%±2.71%(P<0.01),66.76%±2.25%(P<0.01) respectively, compared with that of the control (39.66%±2.01%).After48h treatment with various concentrations of TNSE (62.5μg/mL,125μg/mL,and250μg/mL),the apoptosis rates of LOVO cell were12.8%±1.58%(P<0.05),19.9%±2.16%,(P<0.01)and29.57%±2.76%(P<0.01), respectively, compared with that of the control(7.3%±1.06%).The proportion of G1cells was45.45%±2.54%(P<0.05),56.13%±2.54%(P<0.01),66.05%±2.54%(P<0.01) respectively, compared with that of the control (40.02%±0.69%).RT-PCR demonstrated that NF-κB mRNA expression was significantly downregulated in Raji cells treated with250μg/mL TNSEs for48h (P<0.05), while Bad, caspase-9and caspase-3mRNA levels were upregulated (P<0.05). Moreover, TNSEs treatment resulted in down-regulation of NF-κB protein expression and strikingly up-regulated proteins expression of Bad, cleaved caspase-9, cleaved caspase-3in a dose-dependent manner, as determined by western blot.Furthermore,the similar results were found in LOVO cells treated with125μg/mL TNSEs for48h. The mRNA expression of PI3K, AKT, mTOR, P70s6k1was significantly downregulated (P<0.05), while caspase-9and caspase-3mRNA levels were upregulated (P<0.05,), which was accompanied by significantly down-regulation of the proteins of PI3K,p-AKT,p-mTOR, p-P70s6k1and strikingly up-regulation of the proteins of cleaved caspase-9, cleaved caspase-3in a dose-dependent fashion, as determined by western blot.
There is no any toxicity at the maximum administration40000mg/kg for the mice, so40000mg/kg is safe dose and used for the next experiments. The inhibition rate of the implanted tumor in these three groups(high dosage group,middle dosage group,low dosage group)was67.11%,48.68%,36.84%respectively.The proteins expression of PI3K, p-Akt, p-mTOR,p-P70S6K1, VEGF,CD31were decreased and that of caspase-9,caspase-3were increased in implanted tumor of nude mouse treated with different concentration TNSEs as detected with IHC. Further-moer,TNSEs could regulate the nude mouses'immunity through upragulating Th1cytockines including IL-2, IL-12and down-regulating Th2cytockines, including IL-6IL-10, rectifying the drift of Thl/Th2,which was also in a dose dependant manner.
Conclusion:
1TNSEs could reduce proliferation, cause apoptosis and cell-cycle arrest in Raji cells and LOVO cells, which might be associated with the regulation of PI3K/AKT signaling pathway from two levels of gene transduction and protein expression.
2TNSEs inhibited the growth of implanted tumor of nude mouse which was increasingly associated with regulating multiple molecules in the P3K/AKT pathway and with rectifying the drift of Thl/Th2.
3TNS is a hopeful classic Chinese Medical Formula for tumor therapy.
方法：应用液相色谱-质谱联用技术测定透脓散总提物成分；MTT法检测不同浓度透脓散提物对不同肿瘤细胞(人淋巴瘤Raji细胞,人肠癌LOVO细胞)的增殖抑制率；流式细胞术检测透脓散提液对Raji细胞和LOVO细胞凋亡率及细胞周期的影响；RT-PCR检测透脓散提取液对Raji细胞和LOVO细胞PI3K/AKT信号通路相关分子(PI3K,Akt,m-TOR, p70S6K1,Bad,NF-KB,caspase9,caspase3)的mRNA的表达；Westernblot法检测透脓散提取液对Raji细胞和LOVO细胞PI3K/AKT信号通路相关分子(PI3K,p-Akt,p-mTOR,p-p70S6K1, p-Bad,NF-KB,caspase9,caspase3)蛋白表达的变化；急性毒性实验检测透脓散用药的安全性；根据荷肠癌LOVO细胞裸鼠移植瘤的体积和移植瘤重量计算透脓散提取液的抑瘤率；HE染色光镜观察肿瘤组织的形态结构。免疫组织化学法检测透脓散提取液对肿瘤组织P13K/AKT信号通路相关分子蛋白的表达：ELISA检测裸鼠血清Th1/Th2型细胞因子的含量。
结果：1透脓散提取液主要的化学成分为：毛蕊异黄酮葡萄糖苷,芒柄花苷洋,川芎内酯Ⅰ,毛蕊异黄酮,芒柄花黄素,黄芪甲苷,藁本内酯,且醇提液的成分明显高于水提液。2透脓散提取液可抑制Raji细胞和LOVO细胞的增殖活性并具有明显剂量和时间依赖性。对Raji细胞的72小时半数抑制率为(Half maximal inhibitory concentration,IC50)817.142μg/mL,对LOVO细胞的48小时IC50为：347.603μg/mL (258.526μg/mL to471.545μg/mL)。3透脓散提取液可诱导Raji细胞,LOVO细胞凋亡并阻滞细胞周期在G1期。125μg/mL,250μg/mL和500μg/mL透脓散提取液干预Raji细胞,48h后细胞的凋亡率分别为：12.23±1.98%(P<0.05),20.97+3.96%(P<0.01)和30.4±4.87%(P<0.01),与空白对照组6.02±1.01%相比具有显著的统计学意义。G1期的比例逐渐增高,分别为：44.80%±2.36%(P<0.05),55.48%+2.71%(P<0.01),66.76%±2.25%(P<0.01)与对照组39.66%±2.01%相比具有统计学意义。应用62.5μg/mL,125μg/mL,250μg/mL透脓散醇提液干预LOVO细胞48h后,LOVO细胞的凋亡率分别为：12.8%±1.58%(P<0.05),19.9%±2.16%,(P<0.01),29.57±2.76%(P<0.01)与对照组(7.3%±1.06%)相比具有显著的统计学意义。G1期细胞的比例逐渐增多,分别为：45.45%±2.54%(P<0.05),56.13%±2.54%(P<0.01),66.05%+2.54%(P<0.01)与对照组40.02%＋0.69%相比具有统计学意义。250μg/mL透脓散提取物干预Raji细胞48小时后明显降低Raji细胞NF-κB mRNA及蛋白的表达,增加Bad, caspase-9, caspase-3mRNA及蛋白的表达且具有明显的剂量依赖性。125μg/mL透脓散醇提液干预LOVO细胞48小时后明显降低PI3K, AKT, mTOR, p70s6kl mRNA表达,而Caspase-9,Caspase-3mRNA表达明显增加,PI3K, p-AKT, p-mTOR, p-p70s6kl蛋白表达降低,而Caspase-9, Caspase-3蛋白表达增加,同样具有明显的剂量依赖性。
透脓散提取液最大给药量40000mg/kg时对裸鼠未见明显毒性。高、中、低剂量组的透脓散提取液抑瘤率分别为：67.11%、48.68%、36.84%。免疫组化显示透脓散组P13K,p-Akt, p-mTOR, p-P70S6K1, VEGF, CD31蛋白表达降低,caspase-9, caspase-3蛋白表达增加,且随着剂量的增高,作用逐渐增强。此外,透脓散能调节移植瘤裸鼠的免疫功能,上调Thl型细胞因子(IL-2,IL-12),下调Th2型细胞因子(IL-6,IL-10),从而纠正移植瘤裸鼠机体Thl/Th2漂移,且此效应具有明显的剂量依赖性。
结论：1透脓散提取液可从基因转录和蛋白表达两个层面调控PI3K/AKT信号转导通路中多个分子的表达,从而发挥其抑制Raji细胞、LOVO细胞的增殖,诱导细胞凋亡,阻滞细胞停滞在G1期的作用。
2透脓散提取液可能通过调控PI3K/AKT信号转导通路中多个分子的表达、纠正移植瘤裸鼠的Th1/Th2漂移从而发挥抑制LOVO裸鼠移植瘤的生长的作用。
3透脓散可作为一种有潜力治疗恶性肿瘤的经典方剂。
AIM:To investigate the anti-cancer effects of Tou Nong San extracts (TNSEs) and its possible mechanism.
METHODS:LC-MS Assay for TNS extract. The cytotoxic effect of TNSE on Raji cells and LOVO cells was measured by3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and apoptosis were determined by flow cytometry(FCM).The molecular mechanisms of TNSE-mediated apoptosis were further investigated by reverse transcription-polymerase chain reaction (RT-PCR) analysis of the mRNA expression of nuclear factor-KB (NF-κB), Bcl-xL and Bcl-2-associated death promoter (Bad), caspase-9and caspase-3,PI3K, Akt, mTOR, p70s6k1, and by Western blotting to detect the proteins expression of NF-κB, Bad,PI3K,p-Akt, p-mTOR, p-p70s6k1, caspase-9, caspase-3.The safty of TNSEs was detected by acute toxicity testing.The inhibition ratio was gained on the base of the weight and volume of transplanted tumor, morphosis of tumor was detected by hematoxylin and eosin (HE)stain, the proteins expression of PI3K,p-Akt,p-mTOR,p-p70s6k1, caspase-9, caspase-3,VEGF,CD31were detect by immuno-histochemical(IHC) method and the content of cytokine of Thl/Th2was tested by Enzyme-Linked Immunosorbent Assay(ELISA).
RESULTS:The contents of7major components in TNSEs were Calycosin-7-O-b-D-glucoside, Formononetin-7-O-b-D-glucoside senkyunolide I, Calycosin,formononetin, Astragaloside IV, Z-Ligustilide.TNSEs inhibited Raji cells and LOVO cells proliferation in dose-and time-dependent manners. The Half maximal inhibitory concentration(IC50) of Raji cells was817.142μg/mL at72h,and that of LOVO cells was347.603μg/mL at48h. The apoptosis and Glaresst of these two cell lines were found after treated with TNSEs. After48h treatment with various concentrations of TNSEs (125,250and500μg/mL), the apoptosis rates of Raji cells were12.23±1.98%(P<0.05),20.97±3.96%(P<0.01) and30.4±4.87%(P<0.01), respectively, compared with that of the control (6.02±1.01%).and the G1arrest was also found that was The proportion of G1cells was44.80%±2.36%(P<0.05),55.48%±2.71%(P<0.01),66.76%±2.25%(P<0.01) respectively, compared with that of the control (39.66%±2.01%).After48h treatment with various concentrations of TNSE (62.5μg/mL,125μg/mL,and250μg/mL),the apoptosis rates of LOVO cell were12.8%±1.58%(P<0.05),19.9%±2.16%,(P<0.01)and29.57%±2.76%(P<0.01), respectively, compared with that of the control(7.3%±1.06%).The proportion of G1cells was45.45%±2.54%(P<0.05),56.13%±2.54%(P<0.01),66.05%±2.54%(P<0.01) respectively, compared with that of the control (40.02%±0.69%).RT-PCR demonstrated that NF-κB mRNA expression was significantly downregulated in Raji cells treated with250μg/mL TNSEs for48h (P<0.05), while Bad, caspase-9and caspase-3mRNA levels were upregulated (P<0.05). Moreover, TNSEs treatment resulted in down-regulation of NF-κB protein expression and strikingly up-regulated proteins expression of Bad, cleaved caspase-9, cleaved caspase-3in a dose-dependent manner, as determined by western blot.Furthermore,the similar results were found in LOVO cells treated with125μg/mL TNSEs for48h. The mRNA expression of PI3K, AKT, mTOR, P70s6k1was significantly downregulated (P<0.05), while caspase-9and caspase-3mRNA levels were upregulated (P<0.05,), which was accompanied by significantly down-regulation of the proteins of PI3K,p-AKT,p-mTOR, p-P70s6k1and strikingly up-regulation of the proteins of cleaved caspase-9, cleaved caspase-3in a dose-dependent fashion, as determined by western blot.
There is no any toxicity at the maximum administration40000mg/kg for the mice, so40000mg/kg is safe dose and used for the next experiments. The inhibition rate of the implanted tumor in these three groups(high dosage group,middle dosage group,low dosage group)was67.11%,48.68%,36.84%respectively.The proteins expression of PI3K, p-Akt, p-mTOR,p-P70S6K1, VEGF,CD31were decreased and that of caspase-9,caspase-3were increased in implanted tumor of nude mouse treated with different concentration TNSEs as detected with IHC. Further-moer,TNSEs could regulate the nude mouses'immunity through upragulating Th1cytockines including IL-2, IL-12and down-regulating Th2cytockines, including IL-6IL-10, rectifying the drift of Thl/Th2,which was also in a dose dependant manner.
Conclusion:
1TNSEs could reduce proliferation, cause apoptosis and cell-cycle arrest in Raji cells and LOVO cells, which might be associated with the regulation of PI3K/AKT signaling pathway from two levels of gene transduction and protein expression.
2TNSEs inhibited the growth of implanted tumor of nude mouse which was increasingly associated with regulating multiple molecules in the P3K/AKT pathway and with rectifying the drift of Thl/Th2.
3TNS is a hopeful classic Chinese Medical Formula for tumor therapy.
引文
1 Kundu JK, Surh YJ. Inflammation:Gearing the journey to cancer.Mutat Res.2008;659(1/2):15.
2章锁江.炎症也可促使癌肿发生、发展与转移.实用肿瘤杂志.2010；25(4)：373-376.
3 Nakamura T,Seto M,Tajika M, et al.Clinical features and prognosis of gastric MALT lymphoma with special reference to responsiveness to H.pylori eradication and API2-MALT1 status.Am J Gastroenterol.2008;103(1):62-70.
4 Kenney S. Theodore E.Woodward Award:development of novel, EBV-targeted therapies for EBV-positive tumors.Trans Am Clin Climatol Assoc.2006;117:55-73.
5 John A. Baron, Robert S, et al. A Randomized Trial of Rofecoxih for the Chemoprevention of Colorectal Adenomas. Gastroenterology,2006; 131:1674-1682.
6周玉霞,于君平,刘秋.透脓散治疗耳前瘘管感染70例分析.实用传统中医内科杂志.2003；17(3)：206.
7许金珠,潘成平.透脓散加味治疗慢性附件炎性包块100例.中国民间疗法.2001；9(10)：43-44.
8谢新生,张秀丽,赵家军.穿山甲煎液诱导HL-60细胞凋亡的研究.浙江中西医结合杂志.2001；8(11)：477-479.
9 Rittenhouse JR,Lui PD,Lau BH.Chinese medicinal herbs reverse macrophage suppression induced by urological tumors.J Urol.1991;146(2):486-490.
10 Tin MM,Cho CH,Chan K,et al.Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft. Carcinogenesis.2007;28(6):1347-1355.
11 Fu YS,Lin YY,Chou SC, et al.Tetramethylpyra-zine inhibits activities of glioma cells and glutamate neuro-excito-toxicity:Potential therapeutic application for treatment of gliomas.Neuro Oncol.2008;10(2):139-152.
12 Kan WL,Cho CH,Rudd JA,et al.Study of the anti-proliferative effects and synergy of phthalides from Angelica sinensis on colon cancer cells. J Ethnopharmacol.2008;120(1):36-43.
13徐哲,赵晓頔,王漪檬等.皂角刺抗肿瘤活性成分的分离鉴定与活性测定.沈阳药科大学学报.2008；25(2)：108-111.
14 Linsalata M,Orlando A,Messa C,et al.Quercetin inhibits human DLD-1 colon cancer cell growth and polyamine biosynthesis.Anticancer Res.2010; 30 (9):3501-3507.
15 Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathwayin cancer.[J].Nat Rev Drug Discov.2009;8(8):627-644.
16 Adams JM, Cory S.The Bcl-2 apoptotic switch in cancer development and therapy.Oncogene.2007;26(9):1324-1337.
17 Levine B, Sinha S,KroemerG. Bcl-2 family members:dual regulators of apoptosis and autophagy.Autophagy.2008;4(5):600-606.
18 Wegener E,Krappmann D.Dynamic protein complexes regulate NF-kappaB signal-ing[J].Handb Exp Pharmacol.2008;(186):237-259.
19方乐堃,曾宇慧.PI3K/Akt/mTOR信号传导通路与泌尿系统肿瘤.国际内科学杂.2007；34(9)：509-513.
20 Park CM, Park MJ, Kwak HJ, Lee HC, Kim MS, Lee SH, Park IC, Rhee CH, Hong SI.Ionizing radiation enhances matrix metallo proteinase-2 secretion and invasion of glioma cells through src/epidermal growth factor receptor-mediated p38/Akt and phosphatidylinositol 3-kinase/Akt signal-ing pathways.Cancer Res.2006;66(17):8511-8519.
21 Kitamura T, Asai N, Enomoto A, Maeda K, Kato T, Ishida M, Jiang P, Watanabe T, Usukura J, Kondo T, Costantini F, Murohara T, Takahashi M.Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin.Nat Cell Biol.2008;10(3):329-337.
1段亚丽,谢梅冬.黄芪化学成分及其有效成分黄芪甲苷含量测定的研究现状.中国兽药杂志.2005；35(3)：35-38.
2陈国辉,黄文风.黄芪的化学成分及药理作用研究进展.中国新药杂志.2008；17(17)：1482-1485.
3卢彦琦,贺学礼.黄芪化学成分及药理作用综述.保定师范专科学校学报.2004；17(4)：40-42.
4黄玫,曲晶,李晓天,等.黄芪化学成分及对心血管系统作用的研究进展.中国老年学杂志.2009；29(11)：1451-1453.
5石海莲,吴大正,胡之璧.黄芪皂苷甲的研究进展.中国药学杂志.2008；43(8)：565-567.
6温宇寒.蒙古黄芪的化学成分研究.中国医科大学硕士学位论文.2008：50.
7Hikino H, Funayama S, Endo K. Hypotensive principle of Astragalus and Hedysarum roots.Planta Med.1976;30(4):297-302.
8云秦川.中药黄芪的药理研究进展.内蒙古中医药.2004；23(6)：33-34
9安松兰,张善玉孙,朴惠顺.1年生黄芪中黄芪多糖对小鼠免疫器官指数的影响.延边大学医学学报.2007；30(1)：195-197.
10翁玲,刘彦,刘学英,等.黄芪多糖粉针剂对小鼠脾细胞分泌细胞因子及NK杀伤能力的影响.中医药学刊.2003；21(9)：1522-1524.
11颜培宇.黄芪多糖注射液对免疫功能低下小鼠血清IL-4和IFN-4影响的实验研究.内蒙古中医药.2007；10：35-36.
12黄宏思,黄卫彤,韦鹏涯.黄芪多糖协同抗癌药物对肿瘤细胞的杀伤作用.中国现代临床医学杂志.2007；6(4)：1-2.
13陈蔚,俞茂华,李益明.黄芪多糖对非肥胖糖尿病鼠胰岛超微结构及氧化凋亡因子表达的影响.复旦学报(医学版).2007；34(2)：269-272.
14刘兵荣,肖瑾,丁新生.黄芪多糖干预实验性脑出血后血肿周围细胞凋亡及核因子κB表达的变化.中国临床康复.2006；10(35)：13-15.
15 HuangC,XuD,XiaQ,WangP,RongC,SuY.Reversalof P-glycoprotein-mediated multidrug resistance of human hepatic cancer cells by Astragaloside II.J Pharm Pharmacol. 2012;64(12):1741-1750.
16 Deng Y,Chen HF.Effects of Astragalus injection and its ingredients on proliferation and Akt phosphorylation of breast cancer cell lines.Zhong Xi Yi Jie He Xue Bao. 2009;7(12):1174-1180.
17 Zhang D, Zhuang Y, Pan J,et al.Investigation of effects and mechanisms of total flavonoids of Astragalus and calycosin on human erythroleukemia cells. Oxid Med Cell Longev. 2012;2012:209843.
18 Cheng H Z.Study evolvement of Danggui. Strait Pharm (海峡药学).2008；20(8)：83-85.
19 Dong ZB, Hong M, Fan HW, et al Studies on the finger prints of Radix Angelica Sinensis.Chin J Exp Tradit Med Form(中国实验方剂学杂志).2004；10：1-3.
20 WangW, ShaM, He F. Studies on HPLC fingerprints of Angelica sinensison sale.Li shi zhen Med Mater Med Res(时珍国医国药).2004；15：741-742.
21孙红梅.当归药材资源调查与品质特征的研究.中国协和医科大学.2010；34-36.
22柳永青.当归的化学成分与生物活性.航空航天医药.2009；20(11)：1005-9334
23冯学花,梁肖蕾.当归化学成分与药理作用的研究进展.广州化工,2012；40(22)：1001-9677
24龙全江,徐茂保,赵海鹰.当归油炒前后挥发油化学成分对比研究.中国中药杂志,2007；31(24)：2085-2087.
25骆传环,崔玉芳,黄荣清,等.当归多糖的制备及抑瘤作用.科学技术与工程.2003；3(6)：51-52.
26郑敏,王亚平.当归多糖对K562细胞增殖抑制与诱导分化的实验研究.中国中西医结合杂志.2002；22(1)：54-57.
27 Lee WH, Jin JS, Tsai WC, et al. Biological inhibitory effects of the Chinese herb danggui on brain astrocytoma. Pathobiology.2006;73(3):141.
28 Tsai NM, Lin SZ, Lee CC, et al. The antitumor effects of Angelica sinensis on malignant brain tumors in vitro and in vivo. Clin Cancer Res.2005; 11(9):3475.
29徐晓玉,陈伟海,叶兰,等.阿魏酸钠和白芍总苷对小鼠H22肿瘤生长与血管内皮细胞.中草药.2007；38(4).570-573.
30 Chen Q C, Lee J. Jin W, et al. Cytotoxic constituents from angelicae sinensis radix.Arch Pharm Res.2007;30(5):565.
31 Kan W L, Cho C H, Rudd J A, et al. Study of the anti-proliferative effects and synergy of phthalides from Angelica sinensis on colon cancer cells.J Ethnopharmacol.2008;120(1):36.
32 Cheng Y L, Wen L C, Lee S C, et al. Acetone extract of Angelica sinensis inhibits proliferation of human cancer cells via inducing cell cycle arrest and apoptosis. Life Sci.2004;75(13):1579.
33李万华,李琴,王小刚,等.皂角刺中黄酮类化学成分的分离鉴定.西安大学学报.2005；35(6)：763-765.
34 Lim JC, Park JH, BudesinskyM, et al. Antimutagenic constituents from the thorns of Gleditsia sinensis.Chem Pharm Bull.2005,53(5):561-564.
35李万华,李琴,王小刚,等.皂角刺中5个白桦脂酸型三萜抗HIV活性研究.西北大学学报(自然科学版).2007；37(3)：401-403.
36徐哲,赵晓由页,王漪檬,等.皂角刺抗肿瘤活性成分的分离鉴定与活性测定.沈阳药科大学 学报.2008；25(2)：108-111.
37王明武.汪达成辨治胃癌的临床经验.江苏中医药.2006；27(9)：18-19.
38熊燕子.中西医结合治疗中晚期肺癌32例疗效观察.湖南中医杂志.2006；22(3)：15-16.
39龙玲,耿果霞,李青旺.皂角刺抑制小鼠宫颈癌U14的生长及对增殖细胞核抗原和p53表达的影响.中国中药杂志.2006；31(2)：150-153.
40刘明华,黄兴武,肖顺汉,等.皂角刺提取物对荷瘤小鼠肿瘤生长及细胞因子的影响.肿瘤防治研究.2009；36(5)：365-367.
41王海燕,郭良淼,何丽娅.槲皮素诱导肿瘤细胞凋亡的相关基因调控.中药药理与临床.2005；21(6)：89-91.
42 Avila MA,Velasco JA,Cansado J,et al. Quereetin mediates the down-regulation of mutant p53 in human breast cancer cell line MDA MB468. Cancer Res.1994;54(9):2424-2428.
43袁丁,熊正国,张长城,等.皂角刺皂苷对前列腺癌PC-3细胞增殖抑制作用的研究.天津医药.2008；36(4)：280-282.
44 Lim JC,Park JH,Budesinsky M,et al. Antimutagenic constituents from the thorns of Gleditsia sinensis. Chem Pharm Bull,2005,53(5):561-564.
45范智超,张志琪.川芎多糖的提取、纯化及抗氧化活性的研究.天然产物研究与开发.2005；17(5)：561-567.
46钟凤林,杨连菊,吉力,等.不同产地和品种川芎中挥发油成分的研究.中国中药杂志.1996；21(3)：147.
47曹凤银,刘文心,温月笙,等.川芎化学成分的研究.中草药.1983；14(6)：1.
48王普善,高宣亮,福山爱保,等.中药川芎的化学成分研究-五种内酯化合物.中草药.1985；16(8)：41.
49温月笙,贺庄容,薛孔方,等.川芎化学成分的研究.中草药.1986；17(3)：26.
50王文祥,顾明,蒋小岗,等.川芎化学成分的研究.中草药.2002；33(1)：4.
51王普善,高宣亮,福山爱保,等.中药川芎的化学成分研究-一种萜类化合物.中草药.1985；16(4)：30.
52肖永庆,李丽,游晓琳,等.川芎化学成分研究.中国中药杂志.2002；27(7)：519.
53 NatioTakash,i Niitsu Kazuak,i et a.l A phthalide and 2-farnesyl-6-metyl benzoquinone from Ligusticum chuanxiong.Phytochemistry.l992;31(5):1787.
54 PengA, Ye H J. Reverse effects of tetramethyl pyrazine on the malignant phenotype of BEL-7402 human hepatocarcinoma cells.Chin J Clini Hepatol.2002; 18(3):157-158.
55梅英,石毓君,左国庆,等.川芎嗪逆转HepG2/ADM细胞多药耐药性的体外研究.中国中药杂志.2004；29(10)：970-973.
56戚晓敏,单根法,张辅贤,等.川芎嗪逆转肺癌细胞株多药耐药性的研究.上海第二医科大学学报.2003；23(suppl)：31.
57范青,范广俊,赵瑾瑶,等.川芎嗪脂质体对人白血病细胞株K562多药耐药逆转作用的研究.中国药师.2004；7(10)：753.
58孙家美.穿山甲鳞甲的氨基酸分析.中药材.1989；12(2)：34-37.
60刘世勤.穿山甲的化学成分.中药通报.1988；13(8)：33-34.
59马雪梅.穿山甲化学成分的研究.药学学报.1988；23(8)：588-592.
60敖保世.穿山甲散治疗卵巢肿瘤八例报告.江西中医药.1981；35.
61谢新生,张秀丽,赵家军,等.穿山甲煎液诱导HL-60细胞凋亡的研究.浙江中西医结合杂志.2001；11(8)：477-479.
62 Lee WH, Jin JS, Tsai WC, et al.Biological inhibitory effects of the Chinese herb danggui on brain astrocytoma. Pathobiology.2006;73(3):141.
63 Tsai N M, Lin S Z, Lee C C, et al.The antitumor effects of Angelica sinensis on malignant brain tumors in vitro and in vivo.Clin Cancer Res.2005;11(9):3475.
1古丽巴哈尔,阿巴拜克力.新疆准噶尔铁线莲不同部位提取液抑菌活性初步研究.食品科学.2010；31(9)：117-119.
2库尔班吐松,展锐,张宏,苏力坦阿巴白克力.顶羽菊抗氧化活性研究.生物技术通讯.2010；21(3)：406-412.
3尉小慧,陈玥,夏广新,沈敬山.越鞠丸醇提物与水提物对抑郁模型小鼠的抗抑郁作用比较.上海中医药杂志.2006；40(8)：69-70.
4李长印,谷雨,刘沈林,周玲,居文政,谈恒山.时珍国医国药.2012；23(6)：1458-1460.
5毕炜.中药抗肿瘤多靶点效应的研究进展.江苏中医药.2011；43(3)：92.
6 Zhang D, Zhuang Y, Pan J,et al.Investigation of effects and mechanisms of total flavonoids of Astragalus and calycosin on human erythroleukemia cells.Oxid Med Cell Longev.2012; 2012: 209843.
7 Kan WL, Cho CH, Rudd JA, Lin G. Study of the anti-proliferative effects and synergy of phthalides from Angelica sinensis on colon cancer cells. J Ethnopharmacol.2008;120(1):36-43.
8林琳,沈洪,王立新.黄芪甲苷、β-榄香烯增强小鼠巨噬细胞免疫功能的体外实验研究.临床检验杂志.2011；29(2)：129-131.
9曹丽萍,沈洪,刘丽,刘云.黄芪甲苷、β-榄香烯对SGC7901胃癌细胞COX-2及PGE2表达的影响.现代中西医结合杂志.2010；19(7)：798-900.
10田彦璋苗青旺赵浩亮李辉宇贺杰峰.黄芪甲苷逆转耐药肝癌细胞株HepG2/GCS多药耐药的研究.中国药物与临床.2011；11(7)：778-779.
11 Seo CS, Li G, Kim CH, Lee CS, Jahng Y, Chang HW, Son JK.Cytotoxic and DNA topoisomerases I and II inhibitory constituents from the roots of Aralia cordata.Arch Pharm Res.2007;30(11):1404-9.
12 Kan WL, Cho CH, Rudd JA, Lin G. Study of the anti-proliferative effects and synergy of phthalides from Angelica sinensis on colon cancer cells. J Ethnopharmacol.2008;30; 120 (1):36-43.
1 Siegel R, Naishadham D, Jemal A. Cancer statistics,2013.CA Cancer J Clin.2013; 63 (1):11-30.
2王聪聪.中国近年癌症发病呈现年轻化-胃癌发病率翻番.中国青年.2013-01-24.
3 Alexa我国恶性肿瘤发病率与死亡率.医学论坛报.2013-01-30.
4房良华.主编.现代肿瘤免疫靶向治疗.东南大学出版社.2010；11：292-295.
5 Furtado M, Rule S.Emerging Pharmacotherapy for Relapsed or Refractory Hodgkin's Lymphoma:Focus on Brentuximab Vedotin. Clin Med Insights Oncol.2012;6:31-39.
6 Cunningham D, Humblet Y, Siena S, et al. Cetuximab monothera-py and cetuximab plus irinotecan in irinotecan-refractory metastat-ic colorectal cancer.N Engl J Med.2004;351:337-345.
7 Van Cutsem, E, K hne C H, Erika H, et al. Cetuximab and Chemotherapy as Initial Treatment for Metastatic Colorectal Cancer.N Engl J Med.2009; 360:1408-1417.
8 Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plusirinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.N Engl J Med.2004;350:2335-2342.
9朴炳奎.恶性淋巴瘤的中医诊治体会.江苏中医药.2008；40(9)：4-6.
10曹洋,罗定新.陈锐深治疗恶性淋巴瘤的经验.中国医药学报.2002；17(6)：363.
11金光虎.恶性淋巴瘤的中医辨证分型治疗.吉林医学信息.2000；6：39.
12高虹,朱晏伟.刘嘉湘教授治疗大肠癌.实用中西医结合杂志,1996；9(10)：630-631.
13邓志红,孙珏.大肠癌中医辨证文献研究.云南中医学院学报.2011；34(2)：54-56.
14王晓戎,袁孝兵,李平,等.大肠癌中医证候分布临床调查研究.长春中医药大学学报.2011；27(3)：377-379.
15张恩欣.周岱翰论治大肠癌经验.实用中医药杂志.2006；22(9)：562.
16杨琳.肿瘤就是体内的痈疽.医疗保健器具.2008；3：61-64.
17 Balkwill F, Mantovani A.Inflammation and cancer:back to Virchow? Lancet.2001; 357(9255):539-45.
18 Lochhead P, ElOmar EM.Helicobacter pylori infection and gastric cancer. Best Pract Res Clin Gastroenterol.2007;21 (2):281-297.
19张丽,竺晓凡,吴克复.EBV与血液系统恶性肿瘤相关性的研究进展.白血病·淋巴瘤.2005；14(2)：116-118.
20 Huhn D,郝连杰.HIV相关的非何杰金淋巴瘤.德国医学(中文版).1995；12(3)：137-139.
21 Munkholm P. Review article:the incidence and prevalence of colo-rectal cancer in inflammatory bowel disease. Aliment Pharmacol Ther,2003,18 (Suppl 2):1-5
22 Eaden JA,Mayberry JF.The risk of colorectal cancer in ulcerative colitis:a meta-analysis. Gut.2001;48(5):526-535.
23 Garcia-Rodriguez LA, Huerta-Alvarez C.Reduced risk of colorectal cancer among long-term users of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs.Epidemiology.2001; 12 (1): 88-93.
24 Baron JA, Sandler RS, Bresalier RS, Quan H, Riddell R, Lanas A, et al. A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology.2006;131(6):1674-1682.
25 Ulrich CM, Bigler J, Potter JD. Non-steroidal anti-inflammatory drugs for cancer prevention: promise,perils and pharmacogenetics.Nat Rev Cancer.2006;6,130-140.
26 Lejeune FJ, Monnier Y, Riiegg C.Complete and long-lasting regression of disseminated multiple skin melanoma metastases under treatment with cyclooxygenase-2 inhibitor. Melanoma Res.2006;16(3):263-265.
27 Cohen S, Stemmer SM, Zozulya G, et al.CF102 an A3 adenosine receptor agonist mediates anti-tumor and anti-inflammatory effects in the liver. J Cell Physiol.2011;226(9):2438-47.
28吕俊华,邱世翠,张连同,等.蒲公英体外抑菌作用研究.时珍国医国药.2002；13(4)：215-216.
29李立顺,时维静,关鸣,等.四倍体蒲公英活性成分比较及体外抑菌作用研究.中国实验方剂学杂志.2008；14(6)：55-58.
30沈敬华,杨丽敏,张林娜,等.五种中药提取物抗肿瘤作用的研究.内蒙古医学院学报.2005；27(4)：300-302.
31徐皓.贯叶连翘的化学成分及药理作用研究.安徽农业科学.2007：35(14)：4219-4221.
32王宇翎,张艳,方明,等.白花蛇舌草总黄酮的抗炎及抗菌作用.中国药理学通报.2005；21(3)：348-350.
33朱立俏.白花蛇舌草的化学成分和抗肿瘤活性的研究进展.化工时刊.2012；26(10)：37-41.
34谢新生,张秀丽,赵家军.穿山甲煎液诱导HL-60细胞凋亡的研究.浙江中西医结合杂志.2001；8(11)：477-479.
35 Rittenhouse JR,Lui PD,Lau BH.Chinese medicinal herbs reverse macrophage suppression induced by urological tumors.J Urol.1991;146(2):486-490.
36 Tin MM,Cho CH,Chan K,et al.Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft. Carcinogenesis.2007;28(6):1347-1355.
37 Fu YS,Lin YY,Chou SC, et al.Tetramethylpyra-zine inhibits activities of glioma cells and glutamate neuro-excito-toxicity:Potential therapeutic application for treatment of gliomas.Neuro Oncol.2008; 10(2):139-152.
38. Kan WL,Cho CH,Rudd JA,et al.Study of the anti-proliferative effects and synergy of phthalides from Angelica sinensis on colon cancer cells. J Ethnopharmacol.2008;120(1):36-43.
39.徐哲,赵晓崸，王漪檬,等.皂角刺抗肿瘤活性成分的分离鉴定与活性测定.沈阳药科大学学报.2008；25(2)：108-111.
40.Linsalata M,Orlando A,Messa C,et al.Quercetin inhibits human DLD-1 colon cancer cell growth and polyamine biosynthesis.Anticancer Res.2010; 30 (9):3501-3507.
41黄波,郎贤平,王晓东.川芎嗪、顺铂对人小细胞肺癌NCI-H446细胞凋亡的影响及机制探讨.山东医药.2011；51(18)：5-6.
42刘文松,燕海姣,朱峰,江勇.顺铂诱导肝癌细胞凋亡过程中的Survivin表达变化及意义.现代肿瘤医学.2011；11(19)：2168-2170.
43柳友清,邢辉,韩晓兵,等.顺铂诱导宫颈癌Hela细胞凋亡及其作用机制的研究.中国肿瘤临床.2006；33(1)：1-4.
44张丽杰,武湘云,赵振军.顺铂诱导人卵巢癌细胞系HO-8910细胞凋亡.中国肿瘤.2004；13(4)：261-263.
45罗静,叶兴伟,蒋文,等.阿糖胞苷诱导人MDS细胞株MUTZ-8细胞凋亡过程中活性氧水平的变化.第三军医大学学报.2012；34(15)：1492-1495.
46刘兴元,曾国芳,谢晓恬.阿糖胞苷对HL60细胞增殖和凋亡及bcl-2基因表达的影响.上海医学2006；29(3)：180-184.
47杨培民,代龙,李钦青,曹广尚,魏永利.白花蛇舌草多糖对人宫颈癌Hela细胞和人肝癌Bel-7402细胞生长的影响.现代中药研究与实践.2010；24(3)：32-34.
48曾炜炜,钱江潮,周海霞,王菊香,李原,章佳珠.当归多糖诱导K562白血病细胞凋亡的实验研究.现代中西医结合杂志.2007.16(2)：165-166,170.
49胡家才,李清泉.川芎嗪对肺癌A549细胞增殖与凋亡的影响及其机制.武汉大学学报(医学版).2010；31(1)：19-21,50.
50李玉芳,仲宁,沈文香,王金志.姜黄素诱导人胃癌SGC-7901细胞凋亡.江苏医药.2010；36(11)：1278-1280.
51胡海霞,郑良朴,陈文列,等.解毒消癥饮对BGC-823胃腺癌细胞线粒体膜电位与细胞凋亡的影响.中国肿瘤.2010；19(5)：338-342.
52Liu P,Cheng H,RobertsTM, et al.Targeting the phosphoinositide 3-kinase pathwayin cancer. Nat Rev Drug Discov.2009;8(8):627-644.
53 Liu P,Cheng H,Roberts TM,et al.Targeting the phosphoinositide 3-kinase pathwayin cancer. Nat Rev Drug Discov.2009;8(8):627-644.
54 Adams JM, Cory S.The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 2007;26(9):1324-1337.
55 Levine B, Sinha S,KroemerG. Bcl-2 family members:dual regulators of apoptosis and autophagy.Autophagy.2008;4(5):600-606.
56 Wegener E,Krappmann D.Dynamic protein complexes regulate NF-kappaB signaling. Handb Exp Pharmacol.2008;(186):237-259.
57 Liu P,Cheng H,Roberts TM,Zhao JJ.Targeting the phosphoinositide 3-kinase pathway in cancer.Nat Rev Drug Discov.2009;8:627-644.
58 Li Q, Verma IM.NF-kappaB regulation in the immune system.Nat Rev Immunol.2002; 2: 725-734.
59.Jost PJ, Ruland J.Aberrant NF-B signaling in lymphoma:mechanisms, consequences, and therapeutic implications. Blood.2007; 109:2700-2707.
60. Espinosa I, Briones J, Bordes R, Brunet S, Martino R, Sureda A, et al.Activation of the NF-kappaB signalling pathway in diffuse large B-cell lymphoma:clinical implications. Histopathology.2008;53:441-449.
61. Heckman CA, Cao T, Somsouk L, Duan H, Mehew JW, Zhang CY, et al. Critical elements of the immunoglobulin heavy chain gene enhancers for deregulated expression of bcl-2.Cancer Res.2003;63:6666-6673.
62.Zhou H, Du MQ, Dixit VM. Constitutive NF-kappaB activation by the t(11; 18)(q21;q21) product in MALT lymphoma is linked to deregulated ubiquitin ligase activity.Cancer Cell.2005;7:425-431.
63. Zhang H, Yan D, Shi X, Liang H, Pang Y, Qin N,et al. Transmembrane TNF-alpha mediates "forward" and "reverse" signaling, inducing cell death or survival via the NF-kappaB pathway in Raji Burkitt lymphoma cells. J Leukoc Biol.2008;84:789-797.
64. Pham LV, Tamayo AT, Yoshimura LC, Lo P, Ford RJ.Inhibition of constitutive NF-kappa B activation in mantle cell lymphoma B cells leads to induction of cell cycle arrest and apoptosis. J Immunol.2003;171:88-95.
65 Fu L, Lin-Lee YC, Pham LV, Tamayo A, Yoshimura L, Ford RJ. Constitutive NF-kappaB and NFAT activation leads to stimulation of the BLyS survival pathway in aggressive B-cell lymphomas. Blood.2006;107:4540-4548.
66.Keutgens A, Robert I, Viatour P, Chariot A.Deregulated NF-kappaB activity in haematological malignancies. Biochem Pharmacol.2006;72:1069-1080.
67.Prashant Bavi, Shahab Uddin, Rong Bu, Maqbool Ahmed, Jehad Abubaker, Valorie Balde,et al. The biological and clinical impact of inhibition of NF-KB-initiated apoptosis in diffuse large B cell lymphoma (DLBCL). J Pathol.2011;224:355-366.
68 Jeong SY,Seol DW.The role of mitochondria in apoptosis. BMB Rep.2008; 41:11-22.
69.Thees S, Hubbard GB, Winckler J, Schultz C,Rami A. Specific alteration of the Bax/Bcl2 ratio and cytochrome c without execution of apoptosis in the hippocampus of aged baboons. Restor Neurol Neurosci.2005;23:1-9.
70.Martinou JC,Green DR.Breaking the mitochondrial barrier.Nat Rev Mol Cell Biol. 2001;2:63-67.
71. Lazebnik YA,Kaufmann SH,Desnoyers S,Poirier GG,Earnshaw WC. Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature. 1994;371:346-347.
72. Juin P, Geneste O, Raimbaud E, Hickman JA. Shooting at survivors:Bcl-2 family members as drug targets for cancer. Biochim Biophys Acta.2004; 1644:251-260.
73.Reed JC, Pellecchia M. Apoptosis-based therapies for hematologic malignancies. Blood. 2005;106:408-418.
74.Zimmermann KC, Bonzon C,Green DR.The machinery of programmed cell death. Pharmacol Ther.2001;92:57-70.
75. Ranger AM, Zha J, Harada H,et al. Bad-deficient mice develop diffuse large B cell lymphoma. Proc Natl Acad Sci USA.2003;100:9324-9329.
76.Wang JL, Liu D, Zhang ZJ, et al. Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells.Proc Natl Acad Sci USA. 2000;97:7124-7129.
77.Carpten JD, Faber AL, Horn C, et al. A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature.2007;448:439-444.
78.Chen QC, Lee J, Jin W, et al., Cytotoxic constituents from angelicae sinensis radix. Arch Pharm Res.2007;30:565-569.
79.Rychahou PG, Jackson LN, Silva SR,et al.Targeted molecular therapy of the PI3K pathway: therapeutic significance of PI3Ksubunit targeting in colorectal carcinoma. Ann Surg.2006; 243: 833-842;discussion 843-844.
80.Wang J, Kuropatwinski K, Hauser J,et al.Colon carcinoma cells harboring PIK3CA mutations display resistance to growth factor deprivation induced apoptosis. Mol Cancer Ther. 2007; 6:1143-1150.
81.Liu Y, Chen L, Ko TC, et al.Evil is a survival factor which conveys resistance to both TGFbeta-and taxol-mediated cell death via PI3K/AKT. Oncogene.2006; 25:3565-3575.
82.Roulin D, Cerantola Y, Dormond-Meuwly A, et al.Targeting mTORC2 inhibits colon cancer cell proliferation in vitro and tumor formation in vivo. Mol Cancer.2010; 9:57.
83.Mikami I, Zhang F, Hirata T, et al.Inhibition of activated phosphatidylinositol 3-kinase/AKT pathway in malignant pleural mesothelioma leads to G1 cell cycle arrest. Oncol Rep.2010; 24: 1677-1681.
84.Dituri F, Mazzocca A, Lupo L, et al.,PI3K class IB controls the cell cycle checkpoint promoting cellproliferation in hepatocellular carcinoma. Int J Cancer.2012;130:2505-2513.
85.Brown RE, Tan D, Taylor JS, et al.Morphoproteomic confirmation of constitutively activated mTOR, ERK, and NF-kappaB pathways in high risk neuro-blastoma, with cell cycle andprotein analyte correlates. Ann Clin Lab Sci.2007;37:141-147.
86.Gao N, Zhang Z, Jiang BH,et al. Role of PI3K/AKT/mTOR signaling in the cell cycle progression of human prostate cancer. Biochem Biophys Res Commun.2003; 310:1124-1132.
87.Gao N, Flynn DC, Zhang Z, et al., G1 cell cycle progression and the expression of G1 cyclins are regulated byPI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells. Am JPhysiol Cell Physiol.2004;287:C281-91.
88.Feng W, Duan X, Liu J, et al.Morphoproteomic evidence of constitutively activated and overexpressed mTOR pathway in cervical squamous carcinoma and high grade squamous intraepithelial lesions. Int J Clin Exp Pathol.2009;2:249-260.
89.Carpten JD, Faber AL, Horn C, et al.,A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature.2007;448:439-444.
90.Brown RE, Zhang PL, Lun M, et al. Morphoproteomic and pharmacoproteomic rationale for mTOR effectors as therapeutic targets in head and neck squamous cell carcinoma. Ann Clin Lab Sci.2006; 36:273-282.
91.Cardone MH, Roy N, Stennicke HR, et al. Regulation of cell death protease caspase-9 by phosphorylation. Science.1998;282:1318-1321.
92.Martinou JC,Green DR.Breaking the mitochondrial barrier. Nat Rev Mol Cell Biol.2001; 2: 63-67.
93.Lazebnik YA, Kaufmann SH, Desnoyers S,et al. Cleavage of poly (ADP-ribose) polymerase by a proteinase with properties like ICE. Nature.1994; 371:346-347.
1许瑞安,陈凌,肖卫东.分子基因药物学.北京大学医学出版社.2008：526-565.
2徐霞飞,陆茵.中药抗肿瘤血管生成研究进展.现代中药研究与实践.2007；21(1)：61-64.
3张芷旋,周清华.中药抗肺癌血管生成药物的研究进展.中国肺癌杂志.2006；9(1)：96-99.
4 Hurwitz HI, Fehrenbacher L, Hainsworth JD, et al. Bevacizumab in combination with fluorouracil and leucovorin:an active regimen for first line metastatic colorectal cancer. J Clin Oncol.2005;23:3502-3508.
5Kabbinavar FF, Hambleton J, Mass RD, et al. Combined analysis of eficacy:the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol.2005;23:3706-3712.
6 Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med.2004;350:2335-2342.
7 Saltz LB, Clarke S, Diaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer:a randomized phase III study.J Clin Oncol.2008;26:2013-2039.
8 Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med,2006,355:2542-2550.
9 Gilbert R, Wang M, Aldape K,etal. RTOG 0625:A phase Ⅱ study of bevacizumab with irinotecan in recurrent glioblastoma (GBM).2009 ASCO Annual Meeting, Abstract No:2001. [http://www.asco.org/, RTOG 0625]
lORini BI, Halabi S, Rosenberg JE,et al.Bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in patients with metastatic renal cell carcinoma:Results of overall survival for CALGB 90206. J Clin Oncol.2010;13 (28):2137-2143.
11 Garcia AA, Hirte H, Fleming G,et al. Phase Ⅱ Clinical Trial of Bevacizumab and Low-Dose Metronomic Oral Cyclophosphamide in Recurrent Ovarian Cancer:A Trial of the California, Chicago, and Princess Margaret Hospital Phase Ⅱ Consortia.J Clin Oncol.2008;26(1):76-82.
12庄洪军,张全安,赵伟.血管内皮生长因子及其受体与肝癌治疗的研究进展.肿瘤研究与临床.2008；6：1618-1621.
13何立丽,苏航,张伟京,等.血管内皮细胞生长因子与抗肿瘤转移治疗的研究.国外医学药学分册.2006；33：2118-2121.
14何振辉,梁念慈.以VEGF和bFGF及其受体为靶点的抗肿瘤血管治疗.国外医学生理病理科学与临床分册.2004；24：162-166.
15张前,牛欣,闫妍,等.羟基红花黄色素A抑制新生血管形成的机制研究.北京中医药大学学报.2004；27(3)：25-29.
16徐晓玉,严鹏科,陈刚,等.川芎嗪对小鼠肺癌血管生长和VEGF表达的抑制.中国药理学通报.2004；20(2)：151-156.
17崔国惠,陈卫华,陈燕.姜黄素和肿瘤坏死因子α调节淋巴瘤细胞VEGF的表达及抗血管形成的研究[J].中国医院药学杂志.2008；28(22)：1918-1922.
18辛颖,倪劲松,王心蕊,等.20(S)-人参皂苷Rg3抗B16黑色素瘤转移的作用.吉林大学学报医学版.2004；30(4)：540-542.
19,张丰华,黄秀深,张萍.小柴胡汤对HL-60白血病细胞株体外分化的诱导作用研究.时珍国医国药.2009；(10).2657-2658
20韩燕,刘经选.天龙合剂对小鼠人胃癌细胞肿瘤生长及肿瘤血管生成的抑制作用.河北中医.2008；(8).874-876
21 ZhangL, Han Y, Wu F, et al. Expression and Clinical Significance of CD44 V6 and MVD in Human Colorectal Carcinoma.Practical Journal of Cancer.2004; 19(5):485-487.
22 Raspollini MR,Amunni G,Villanucci A,et al. Prognostic significance of micro vessel density and vascular endothelial growth factor expression in advcanced serous carcinoma. Int J Gynecol Cancer.2004; 14(5):815-823.
23 Maggi E, Parronchi P, Manetti R, et al. Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Thl andTh2 clones.J Immunol.1992; 148 (7):2142-2147.
24 Jarnicki AG, Lysaght J, Todryk S, et al. Suppression of antitumor immunity by IL-10 and TGF-beta-producing T cells infiltrating the growing tumor:influence of tumor environment on the induction ofCD4+and CD8+regulatoryT cells J Immunol.2006; 177(2):896-904.
25 JonuleitH, SchmittE. The regulatory T cell family:Distinct subsets and their interrelations.J Immunol.2003;171(12):6323-6327.
26 Steinbrink K, Graulich E, Kubsch S, et al.CD4(+)and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. Blood. 2002;99(7):2468-2476.
27 KishimotoT. Interleukin-6:from basic science tomedicine:40 years in immunology. Annu Rev Immunol.2005;23:1-21.
28 Hodge DR, HurtEM, FarrarWL. The role of IL6 and STAT3 in inflammation and cancer. Eur J Cancer.2005;41:2502-2512.
29 TchirkovA, KhalilT, Chautard E,et al. Interleukin-6 gene amplifi-cation and shortened survival in glioblastoma patients. Br J Cancer.2007;96:474-476.
30 Heriuchi Y,Hanazawa A,Nakajima Y,et al. T-helper Th1, Th2 imbalance in the peripheral blood of dog with malignant tumor.Microbiol Immunol.2007;51:1135-1138.
31 Sakaguchi E,Kayano K,Segawa M. Th1/Th2 imbalance in HCV-related liver cirrhosis. Nippon Rinsho.2001;59 (7):1259-1263.
32叶欣,李毅,刘忠民,等.大肠癌患者血清IL-10水平测定及其意义.肿瘤研究与临床.2002；14：171-173.
33 IndrovaM, BieblovaJ, Bubenik J, et al.IL-12 immunotherapy of minimal residual disease inmurinemodels of HPV16-associated tumours:induction of immune responses, cytokine production and kinetics of immune cell subsets.Int J Oncol.2008;32(2):499-507.
34 CarpentierAF. Cancer immunotherapy with Cp G-ODN.Med Sci (Paris),2005,21 (73):77.
35 Wu Y, Wan T, Zhou X, et al. Hsp70-like protein 1 fusion protein enhances induction of carcinoembryonic antigen-specific CD8+CTL response by dendritic cell vaccine. CancerRes. 2005;65:4947-4954.
36朱世杰,于莉莉,贾立群,等.参芪扶正注射液对荷瘤动物生存期影响的免疫机制研究.中华肿瘤防治杂志.2009；16(4)：264-266.
37丁治国,史晓光,汪唐顺,等.流式微球技术检测参芪扶正注射液对化疗小鼠Th1/Th2平衡状态的影响.中国实验方剂学杂志.2009；15(5)：39-41.
38伍杨,邓明会.长叶胡颓子对荷瘤鼠细胞免疫功能影响.中国公共卫生.2010；26(5)：576-577.
2章锁江.炎症也可促使癌肿发生、发展与转移.实用肿瘤杂志.2010；25(4)：373-376.
3 Nakamura T,Seto M,Tajika M, et al.Clinical features and prognosis of gastric MALT lymphoma with special reference to responsiveness to H.pylori eradication and API2-MALT1 status.Am J Gastroenterol.2008;103(1):62-70.
4 Kenney S. Theodore E.Woodward Award:development of novel, EBV-targeted therapies for EBV-positive tumors.Trans Am Clin Climatol Assoc.2006;117:55-73.
5 John A. Baron, Robert S, et al. A Randomized Trial of Rofecoxih for the Chemoprevention of Colorectal Adenomas. Gastroenterology,2006; 131:1674-1682.
6周玉霞,于君平,刘秋.透脓散治疗耳前瘘管感染70例分析.实用传统中医内科杂志.2003；17(3)：206.
7许金珠,潘成平.透脓散加味治疗慢性附件炎性包块100例.中国民间疗法.2001；9(10)：43-44.
8谢新生,张秀丽,赵家军.穿山甲煎液诱导HL-60细胞凋亡的研究.浙江中西医结合杂志.2001；8(11)：477-479.
9 Rittenhouse JR,Lui PD,Lau BH.Chinese medicinal herbs reverse macrophage suppression induced by urological tumors.J Urol.1991;146(2):486-490.
10 Tin MM,Cho CH,Chan K,et al.Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft. Carcinogenesis.2007;28(6):1347-1355.
11 Fu YS,Lin YY,Chou SC, et al.Tetramethylpyra-zine inhibits activities of glioma cells and glutamate neuro-excito-toxicity:Potential therapeutic application for treatment of gliomas.Neuro Oncol.2008;10(2):139-152.
12 Kan WL,Cho CH,Rudd JA,et al.Study of the anti-proliferative effects and synergy of phthalides from Angelica sinensis on colon cancer cells. J Ethnopharmacol.2008;120(1):36-43.
13徐哲,赵晓頔,王漪檬等.皂角刺抗肿瘤活性成分的分离鉴定与活性测定.沈阳药科大学学报.2008；25(2)：108-111.
14 Linsalata M,Orlando A,Messa C,et al.Quercetin inhibits human DLD-1 colon cancer cell growth and polyamine biosynthesis.Anticancer Res.2010; 30 (9):3501-3507.
15 Liu P, Cheng H, Roberts TM, Zhao JJ. Targeting the phosphoinositide 3-kinase pathwayin cancer.[J].Nat Rev Drug Discov.2009;8(8):627-644.
16 Adams JM, Cory S.The Bcl-2 apoptotic switch in cancer development and therapy.Oncogene.2007;26(9):1324-1337.
17 Levine B, Sinha S,KroemerG. Bcl-2 family members:dual regulators of apoptosis and autophagy.Autophagy.2008;4(5):600-606.
18 Wegener E,Krappmann D.Dynamic protein complexes regulate NF-kappaB signal-ing[J].Handb Exp Pharmacol.2008;(186):237-259.
19方乐堃,曾宇慧.PI3K/Akt/mTOR信号传导通路与泌尿系统肿瘤.国际内科学杂.2007；34(9)：509-513.
20 Park CM, Park MJ, Kwak HJ, Lee HC, Kim MS, Lee SH, Park IC, Rhee CH, Hong SI.Ionizing radiation enhances matrix metallo proteinase-2 secretion and invasion of glioma cells through src/epidermal growth factor receptor-mediated p38/Akt and phosphatidylinositol 3-kinase/Akt signal-ing pathways.Cancer Res.2006;66(17):8511-8519.
21 Kitamura T, Asai N, Enomoto A, Maeda K, Kato T, Ishida M, Jiang P, Watanabe T, Usukura J, Kondo T, Costantini F, Murohara T, Takahashi M.Regulation of VEGF-mediated angiogenesis by the Akt/PKB substrate Girdin.Nat Cell Biol.2008;10(3):329-337.
1段亚丽,谢梅冬.黄芪化学成分及其有效成分黄芪甲苷含量测定的研究现状.中国兽药杂志.2005；35(3)：35-38.
2陈国辉,黄文风.黄芪的化学成分及药理作用研究进展.中国新药杂志.2008；17(17)：1482-1485.
3卢彦琦,贺学礼.黄芪化学成分及药理作用综述.保定师范专科学校学报.2004；17(4)：40-42.
4黄玫,曲晶,李晓天,等.黄芪化学成分及对心血管系统作用的研究进展.中国老年学杂志.2009；29(11)：1451-1453.
5石海莲,吴大正,胡之璧.黄芪皂苷甲的研究进展.中国药学杂志.2008；43(8)：565-567.
6温宇寒.蒙古黄芪的化学成分研究.中国医科大学硕士学位论文.2008：50.
7Hikino H, Funayama S, Endo K. Hypotensive principle of Astragalus and Hedysarum roots.Planta Med.1976;30(4):297-302.
8云秦川.中药黄芪的药理研究进展.内蒙古中医药.2004；23(6)：33-34
9安松兰,张善玉孙,朴惠顺.1年生黄芪中黄芪多糖对小鼠免疫器官指数的影响.延边大学医学学报.2007；30(1)：195-197.
10翁玲,刘彦,刘学英,等.黄芪多糖粉针剂对小鼠脾细胞分泌细胞因子及NK杀伤能力的影响.中医药学刊.2003；21(9)：1522-1524.
11颜培宇.黄芪多糖注射液对免疫功能低下小鼠血清IL-4和IFN-4影响的实验研究.内蒙古中医药.2007；10：35-36.
12黄宏思,黄卫彤,韦鹏涯.黄芪多糖协同抗癌药物对肿瘤细胞的杀伤作用.中国现代临床医学杂志.2007；6(4)：1-2.
13陈蔚,俞茂华,李益明.黄芪多糖对非肥胖糖尿病鼠胰岛超微结构及氧化凋亡因子表达的影响.复旦学报(医学版).2007；34(2)：269-272.
14刘兵荣,肖瑾,丁新生.黄芪多糖干预实验性脑出血后血肿周围细胞凋亡及核因子κB表达的变化.中国临床康复.2006；10(35)：13-15.
15 HuangC,XuD,XiaQ,WangP,RongC,SuY.Reversalof P-glycoprotein-mediated multidrug resistance of human hepatic cancer cells by Astragaloside II.J Pharm Pharmacol. 2012;64(12):1741-1750.
16 Deng Y,Chen HF.Effects of Astragalus injection and its ingredients on proliferation and Akt phosphorylation of breast cancer cell lines.Zhong Xi Yi Jie He Xue Bao. 2009;7(12):1174-1180.
17 Zhang D, Zhuang Y, Pan J,et al.Investigation of effects and mechanisms of total flavonoids of Astragalus and calycosin on human erythroleukemia cells. Oxid Med Cell Longev. 2012;2012:209843.
18 Cheng H Z.Study evolvement of Danggui. Strait Pharm (海峡药学).2008；20(8)：83-85.
19 Dong ZB, Hong M, Fan HW, et al Studies on the finger prints of Radix Angelica Sinensis.Chin J Exp Tradit Med Form(中国实验方剂学杂志).2004；10：1-3.
20 WangW, ShaM, He F. Studies on HPLC fingerprints of Angelica sinensison sale.Li shi zhen Med Mater Med Res(时珍国医国药).2004；15：741-742.
21孙红梅.当归药材资源调查与品质特征的研究.中国协和医科大学.2010；34-36.
22柳永青.当归的化学成分与生物活性.航空航天医药.2009；20(11)：1005-9334
23冯学花,梁肖蕾.当归化学成分与药理作用的研究进展.广州化工,2012；40(22)：1001-9677
24龙全江,徐茂保,赵海鹰.当归油炒前后挥发油化学成分对比研究.中国中药杂志,2007；31(24)：2085-2087.
25骆传环,崔玉芳,黄荣清,等.当归多糖的制备及抑瘤作用.科学技术与工程.2003；3(6)：51-52.
26郑敏,王亚平.当归多糖对K562细胞增殖抑制与诱导分化的实验研究.中国中西医结合杂志.2002；22(1)：54-57.
27 Lee WH, Jin JS, Tsai WC, et al. Biological inhibitory effects of the Chinese herb danggui on brain astrocytoma. Pathobiology.2006;73(3):141.
28 Tsai NM, Lin SZ, Lee CC, et al. The antitumor effects of Angelica sinensis on malignant brain tumors in vitro and in vivo. Clin Cancer Res.2005; 11(9):3475.
29徐晓玉,陈伟海,叶兰,等.阿魏酸钠和白芍总苷对小鼠H22肿瘤生长与血管内皮细胞.中草药.2007；38(4).570-573.
30 Chen Q C, Lee J. Jin W, et al. Cytotoxic constituents from angelicae sinensis radix.Arch Pharm Res.2007;30(5):565.
31 Kan W L, Cho C H, Rudd J A, et al. Study of the anti-proliferative effects and synergy of phthalides from Angelica sinensis on colon cancer cells.J Ethnopharmacol.2008;120(1):36.
32 Cheng Y L, Wen L C, Lee S C, et al. Acetone extract of Angelica sinensis inhibits proliferation of human cancer cells via inducing cell cycle arrest and apoptosis. Life Sci.2004;75(13):1579.
33李万华,李琴,王小刚,等.皂角刺中黄酮类化学成分的分离鉴定.西安大学学报.2005；35(6)：763-765.
34 Lim JC, Park JH, BudesinskyM, et al. Antimutagenic constituents from the thorns of Gleditsia sinensis.Chem Pharm Bull.2005,53(5):561-564.
35李万华,李琴,王小刚,等.皂角刺中5个白桦脂酸型三萜抗HIV活性研究.西北大学学报(自然科学版).2007；37(3)：401-403.
36徐哲,赵晓由页,王漪檬,等.皂角刺抗肿瘤活性成分的分离鉴定与活性测定.沈阳药科大学 学报.2008；25(2)：108-111.
37王明武.汪达成辨治胃癌的临床经验.江苏中医药.2006；27(9)：18-19.
38熊燕子.中西医结合治疗中晚期肺癌32例疗效观察.湖南中医杂志.2006；22(3)：15-16.
39龙玲,耿果霞,李青旺.皂角刺抑制小鼠宫颈癌U14的生长及对增殖细胞核抗原和p53表达的影响.中国中药杂志.2006；31(2)：150-153.
40刘明华,黄兴武,肖顺汉,等.皂角刺提取物对荷瘤小鼠肿瘤生长及细胞因子的影响.肿瘤防治研究.2009；36(5)：365-367.
41王海燕,郭良淼,何丽娅.槲皮素诱导肿瘤细胞凋亡的相关基因调控.中药药理与临床.2005；21(6)：89-91.
42 Avila MA,Velasco JA,Cansado J,et al. Quereetin mediates the down-regulation of mutant p53 in human breast cancer cell line MDA MB468. Cancer Res.1994;54(9):2424-2428.
43袁丁,熊正国,张长城,等.皂角刺皂苷对前列腺癌PC-3细胞增殖抑制作用的研究.天津医药.2008；36(4)：280-282.
44 Lim JC,Park JH,Budesinsky M,et al. Antimutagenic constituents from the thorns of Gleditsia sinensis. Chem Pharm Bull,2005,53(5):561-564.
45范智超,张志琪.川芎多糖的提取、纯化及抗氧化活性的研究.天然产物研究与开发.2005；17(5)：561-567.
46钟凤林,杨连菊,吉力,等.不同产地和品种川芎中挥发油成分的研究.中国中药杂志.1996；21(3)：147.
47曹凤银,刘文心,温月笙,等.川芎化学成分的研究.中草药.1983；14(6)：1.
48王普善,高宣亮,福山爱保,等.中药川芎的化学成分研究-五种内酯化合物.中草药.1985；16(8)：41.
49温月笙,贺庄容,薛孔方,等.川芎化学成分的研究.中草药.1986；17(3)：26.
50王文祥,顾明,蒋小岗,等.川芎化学成分的研究.中草药.2002；33(1)：4.
51王普善,高宣亮,福山爱保,等.中药川芎的化学成分研究-一种萜类化合物.中草药.1985；16(4)：30.
52肖永庆,李丽,游晓琳,等.川芎化学成分研究.中国中药杂志.2002；27(7)：519.
53 NatioTakash,i Niitsu Kazuak,i et a.l A phthalide and 2-farnesyl-6-metyl benzoquinone from Ligusticum chuanxiong.Phytochemistry.l992;31(5):1787.
54 PengA, Ye H J. Reverse effects of tetramethyl pyrazine on the malignant phenotype of BEL-7402 human hepatocarcinoma cells.Chin J Clini Hepatol.2002; 18(3):157-158.
55梅英,石毓君,左国庆,等.川芎嗪逆转HepG2/ADM细胞多药耐药性的体外研究.中国中药杂志.2004；29(10)：970-973.
56戚晓敏,单根法,张辅贤,等.川芎嗪逆转肺癌细胞株多药耐药性的研究.上海第二医科大学学报.2003；23(suppl)：31.
57范青,范广俊,赵瑾瑶,等.川芎嗪脂质体对人白血病细胞株K562多药耐药逆转作用的研究.中国药师.2004；7(10)：753.
58孙家美.穿山甲鳞甲的氨基酸分析.中药材.1989；12(2)：34-37.
60刘世勤.穿山甲的化学成分.中药通报.1988；13(8)：33-34.
59马雪梅.穿山甲化学成分的研究.药学学报.1988；23(8)：588-592.
60敖保世.穿山甲散治疗卵巢肿瘤八例报告.江西中医药.1981；35.
61谢新生,张秀丽,赵家军,等.穿山甲煎液诱导HL-60细胞凋亡的研究.浙江中西医结合杂志.2001；11(8)：477-479.
62 Lee WH, Jin JS, Tsai WC, et al.Biological inhibitory effects of the Chinese herb danggui on brain astrocytoma. Pathobiology.2006;73(3):141.
63 Tsai N M, Lin S Z, Lee C C, et al.The antitumor effects of Angelica sinensis on malignant brain tumors in vitro and in vivo.Clin Cancer Res.2005;11(9):3475.
1古丽巴哈尔,阿巴拜克力.新疆准噶尔铁线莲不同部位提取液抑菌活性初步研究.食品科学.2010；31(9)：117-119.
2库尔班吐松,展锐,张宏,苏力坦阿巴白克力.顶羽菊抗氧化活性研究.生物技术通讯.2010；21(3)：406-412.
3尉小慧,陈玥,夏广新,沈敬山.越鞠丸醇提物与水提物对抑郁模型小鼠的抗抑郁作用比较.上海中医药杂志.2006；40(8)：69-70.
4李长印,谷雨,刘沈林,周玲,居文政,谈恒山.时珍国医国药.2012；23(6)：1458-1460.
5毕炜.中药抗肿瘤多靶点效应的研究进展.江苏中医药.2011；43(3)：92.
6 Zhang D, Zhuang Y, Pan J,et al.Investigation of effects and mechanisms of total flavonoids of Astragalus and calycosin on human erythroleukemia cells.Oxid Med Cell Longev.2012; 2012: 209843.
7 Kan WL, Cho CH, Rudd JA, Lin G. Study of the anti-proliferative effects and synergy of phthalides from Angelica sinensis on colon cancer cells. J Ethnopharmacol.2008;120(1):36-43.
8林琳,沈洪,王立新.黄芪甲苷、β-榄香烯增强小鼠巨噬细胞免疫功能的体外实验研究.临床检验杂志.2011；29(2)：129-131.
9曹丽萍,沈洪,刘丽,刘云.黄芪甲苷、β-榄香烯对SGC7901胃癌细胞COX-2及PGE2表达的影响.现代中西医结合杂志.2010；19(7)：798-900.
10田彦璋苗青旺赵浩亮李辉宇贺杰峰.黄芪甲苷逆转耐药肝癌细胞株HepG2/GCS多药耐药的研究.中国药物与临床.2011；11(7)：778-779.
11 Seo CS, Li G, Kim CH, Lee CS, Jahng Y, Chang HW, Son JK.Cytotoxic and DNA topoisomerases I and II inhibitory constituents from the roots of Aralia cordata.Arch Pharm Res.2007;30(11):1404-9.
12 Kan WL, Cho CH, Rudd JA, Lin G. Study of the anti-proliferative effects and synergy of phthalides from Angelica sinensis on colon cancer cells. J Ethnopharmacol.2008;30; 120 (1):36-43.
1 Siegel R, Naishadham D, Jemal A. Cancer statistics,2013.CA Cancer J Clin.2013; 63 (1):11-30.
2王聪聪.中国近年癌症发病呈现年轻化-胃癌发病率翻番.中国青年.2013-01-24.
3 Alexa我国恶性肿瘤发病率与死亡率.医学论坛报.2013-01-30.
4房良华.主编.现代肿瘤免疫靶向治疗.东南大学出版社.2010；11：292-295.
5 Furtado M, Rule S.Emerging Pharmacotherapy for Relapsed or Refractory Hodgkin's Lymphoma:Focus on Brentuximab Vedotin. Clin Med Insights Oncol.2012;6:31-39.
6 Cunningham D, Humblet Y, Siena S, et al. Cetuximab monothera-py and cetuximab plus irinotecan in irinotecan-refractory metastat-ic colorectal cancer.N Engl J Med.2004;351:337-345.
7 Van Cutsem, E, K hne C H, Erika H, et al. Cetuximab and Chemotherapy as Initial Treatment for Metastatic Colorectal Cancer.N Engl J Med.2009; 360:1408-1417.
8 Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plusirinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.N Engl J Med.2004;350:2335-2342.
9朴炳奎.恶性淋巴瘤的中医诊治体会.江苏中医药.2008；40(9)：4-6.
10曹洋,罗定新.陈锐深治疗恶性淋巴瘤的经验.中国医药学报.2002；17(6)：363.
11金光虎.恶性淋巴瘤的中医辨证分型治疗.吉林医学信息.2000；6：39.
12高虹,朱晏伟.刘嘉湘教授治疗大肠癌.实用中西医结合杂志,1996；9(10)：630-631.
13邓志红,孙珏.大肠癌中医辨证文献研究.云南中医学院学报.2011；34(2)：54-56.
14王晓戎,袁孝兵,李平,等.大肠癌中医证候分布临床调查研究.长春中医药大学学报.2011；27(3)：377-379.
15张恩欣.周岱翰论治大肠癌经验.实用中医药杂志.2006；22(9)：562.
16杨琳.肿瘤就是体内的痈疽.医疗保健器具.2008；3：61-64.
17 Balkwill F, Mantovani A.Inflammation and cancer:back to Virchow? Lancet.2001; 357(9255):539-45.
18 Lochhead P, ElOmar EM.Helicobacter pylori infection and gastric cancer. Best Pract Res Clin Gastroenterol.2007;21 (2):281-297.
19张丽,竺晓凡,吴克复.EBV与血液系统恶性肿瘤相关性的研究进展.白血病·淋巴瘤.2005；14(2)：116-118.
20 Huhn D,郝连杰.HIV相关的非何杰金淋巴瘤.德国医学(中文版).1995；12(3)：137-139.
21 Munkholm P. Review article:the incidence and prevalence of colo-rectal cancer in inflammatory bowel disease. Aliment Pharmacol Ther,2003,18 (Suppl 2):1-5
22 Eaden JA,Mayberry JF.The risk of colorectal cancer in ulcerative colitis:a meta-analysis. Gut.2001;48(5):526-535.
23 Garcia-Rodriguez LA, Huerta-Alvarez C.Reduced risk of colorectal cancer among long-term users of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs.Epidemiology.2001; 12 (1): 88-93.
24 Baron JA, Sandler RS, Bresalier RS, Quan H, Riddell R, Lanas A, et al. A randomized trial of rofecoxib for the chemoprevention of colorectal adenomas. Gastroenterology.2006;131(6):1674-1682.
25 Ulrich CM, Bigler J, Potter JD. Non-steroidal anti-inflammatory drugs for cancer prevention: promise,perils and pharmacogenetics.Nat Rev Cancer.2006;6,130-140.
26 Lejeune FJ, Monnier Y, Riiegg C.Complete and long-lasting regression of disseminated multiple skin melanoma metastases under treatment with cyclooxygenase-2 inhibitor. Melanoma Res.2006;16(3):263-265.
27 Cohen S, Stemmer SM, Zozulya G, et al.CF102 an A3 adenosine receptor agonist mediates anti-tumor and anti-inflammatory effects in the liver. J Cell Physiol.2011;226(9):2438-47.
28吕俊华,邱世翠,张连同,等.蒲公英体外抑菌作用研究.时珍国医国药.2002；13(4)：215-216.
29李立顺,时维静,关鸣,等.四倍体蒲公英活性成分比较及体外抑菌作用研究.中国实验方剂学杂志.2008；14(6)：55-58.
30沈敬华,杨丽敏,张林娜,等.五种中药提取物抗肿瘤作用的研究.内蒙古医学院学报.2005；27(4)：300-302.
31徐皓.贯叶连翘的化学成分及药理作用研究.安徽农业科学.2007：35(14)：4219-4221.
32王宇翎,张艳,方明,等.白花蛇舌草总黄酮的抗炎及抗菌作用.中国药理学通报.2005；21(3)：348-350.
33朱立俏.白花蛇舌草的化学成分和抗肿瘤活性的研究进展.化工时刊.2012；26(10)：37-41.
34谢新生,张秀丽,赵家军.穿山甲煎液诱导HL-60细胞凋亡的研究.浙江中西医结合杂志.2001；8(11)：477-479.
35 Rittenhouse JR,Lui PD,Lau BH.Chinese medicinal herbs reverse macrophage suppression induced by urological tumors.J Urol.1991;146(2):486-490.
36 Tin MM,Cho CH,Chan K,et al.Astragalus saponins induce growth inhibition and apoptosis in human colon cancer cells and tumor xenograft. Carcinogenesis.2007;28(6):1347-1355.
37 Fu YS,Lin YY,Chou SC, et al.Tetramethylpyra-zine inhibits activities of glioma cells and glutamate neuro-excito-toxicity:Potential therapeutic application for treatment of gliomas.Neuro Oncol.2008; 10(2):139-152.
38. Kan WL,Cho CH,Rudd JA,et al.Study of the anti-proliferative effects and synergy of phthalides from Angelica sinensis on colon cancer cells. J Ethnopharmacol.2008;120(1):36-43.
39.徐哲,赵晓崸，王漪檬,等.皂角刺抗肿瘤活性成分的分离鉴定与活性测定.沈阳药科大学学报.2008；25(2)：108-111.
40.Linsalata M,Orlando A,Messa C,et al.Quercetin inhibits human DLD-1 colon cancer cell growth and polyamine biosynthesis.Anticancer Res.2010; 30 (9):3501-3507.
41黄波,郎贤平,王晓东.川芎嗪、顺铂对人小细胞肺癌NCI-H446细胞凋亡的影响及机制探讨.山东医药.2011；51(18)：5-6.
42刘文松,燕海姣,朱峰,江勇.顺铂诱导肝癌细胞凋亡过程中的Survivin表达变化及意义.现代肿瘤医学.2011；11(19)：2168-2170.
43柳友清,邢辉,韩晓兵,等.顺铂诱导宫颈癌Hela细胞凋亡及其作用机制的研究.中国肿瘤临床.2006；33(1)：1-4.
44张丽杰,武湘云,赵振军.顺铂诱导人卵巢癌细胞系HO-8910细胞凋亡.中国肿瘤.2004；13(4)：261-263.
45罗静,叶兴伟,蒋文,等.阿糖胞苷诱导人MDS细胞株MUTZ-8细胞凋亡过程中活性氧水平的变化.第三军医大学学报.2012；34(15)：1492-1495.
46刘兴元,曾国芳,谢晓恬.阿糖胞苷对HL60细胞增殖和凋亡及bcl-2基因表达的影响.上海医学2006；29(3)：180-184.
47杨培民,代龙,李钦青,曹广尚,魏永利.白花蛇舌草多糖对人宫颈癌Hela细胞和人肝癌Bel-7402细胞生长的影响.现代中药研究与实践.2010；24(3)：32-34.
48曾炜炜,钱江潮,周海霞,王菊香,李原,章佳珠.当归多糖诱导K562白血病细胞凋亡的实验研究.现代中西医结合杂志.2007.16(2)：165-166,170.
49胡家才,李清泉.川芎嗪对肺癌A549细胞增殖与凋亡的影响及其机制.武汉大学学报(医学版).2010；31(1)：19-21,50.
50李玉芳,仲宁,沈文香,王金志.姜黄素诱导人胃癌SGC-7901细胞凋亡.江苏医药.2010；36(11)：1278-1280.
51胡海霞,郑良朴,陈文列,等.解毒消癥饮对BGC-823胃腺癌细胞线粒体膜电位与细胞凋亡的影响.中国肿瘤.2010；19(5)：338-342.
52Liu P,Cheng H,RobertsTM, et al.Targeting the phosphoinositide 3-kinase pathwayin cancer. Nat Rev Drug Discov.2009;8(8):627-644.
53 Liu P,Cheng H,Roberts TM,et al.Targeting the phosphoinositide 3-kinase pathwayin cancer. Nat Rev Drug Discov.2009;8(8):627-644.
54 Adams JM, Cory S.The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 2007;26(9):1324-1337.
55 Levine B, Sinha S,KroemerG. Bcl-2 family members:dual regulators of apoptosis and autophagy.Autophagy.2008;4(5):600-606.
56 Wegener E,Krappmann D.Dynamic protein complexes regulate NF-kappaB signaling. Handb Exp Pharmacol.2008;(186):237-259.
57 Liu P,Cheng H,Roberts TM,Zhao JJ.Targeting the phosphoinositide 3-kinase pathway in cancer.Nat Rev Drug Discov.2009;8:627-644.
58 Li Q, Verma IM.NF-kappaB regulation in the immune system.Nat Rev Immunol.2002; 2: 725-734.
59.Jost PJ, Ruland J.Aberrant NF-B signaling in lymphoma:mechanisms, consequences, and therapeutic implications. Blood.2007; 109:2700-2707.
60. Espinosa I, Briones J, Bordes R, Brunet S, Martino R, Sureda A, et al.Activation of the NF-kappaB signalling pathway in diffuse large B-cell lymphoma:clinical implications. Histopathology.2008;53:441-449.
61. Heckman CA, Cao T, Somsouk L, Duan H, Mehew JW, Zhang CY, et al. Critical elements of the immunoglobulin heavy chain gene enhancers for deregulated expression of bcl-2.Cancer Res.2003;63:6666-6673.
62.Zhou H, Du MQ, Dixit VM. Constitutive NF-kappaB activation by the t(11; 18)(q21;q21) product in MALT lymphoma is linked to deregulated ubiquitin ligase activity.Cancer Cell.2005;7:425-431.
63. Zhang H, Yan D, Shi X, Liang H, Pang Y, Qin N,et al. Transmembrane TNF-alpha mediates "forward" and "reverse" signaling, inducing cell death or survival via the NF-kappaB pathway in Raji Burkitt lymphoma cells. J Leukoc Biol.2008;84:789-797.
64. Pham LV, Tamayo AT, Yoshimura LC, Lo P, Ford RJ.Inhibition of constitutive NF-kappa B activation in mantle cell lymphoma B cells leads to induction of cell cycle arrest and apoptosis. J Immunol.2003;171:88-95.
65 Fu L, Lin-Lee YC, Pham LV, Tamayo A, Yoshimura L, Ford RJ. Constitutive NF-kappaB and NFAT activation leads to stimulation of the BLyS survival pathway in aggressive B-cell lymphomas. Blood.2006;107:4540-4548.
66.Keutgens A, Robert I, Viatour P, Chariot A.Deregulated NF-kappaB activity in haematological malignancies. Biochem Pharmacol.2006;72:1069-1080.
67.Prashant Bavi, Shahab Uddin, Rong Bu, Maqbool Ahmed, Jehad Abubaker, Valorie Balde,et al. The biological and clinical impact of inhibition of NF-KB-initiated apoptosis in diffuse large B cell lymphoma (DLBCL). J Pathol.2011;224:355-366.
68 Jeong SY,Seol DW.The role of mitochondria in apoptosis. BMB Rep.2008; 41:11-22.
69.Thees S, Hubbard GB, Winckler J, Schultz C,Rami A. Specific alteration of the Bax/Bcl2 ratio and cytochrome c without execution of apoptosis in the hippocampus of aged baboons. Restor Neurol Neurosci.2005;23:1-9.
70.Martinou JC,Green DR.Breaking the mitochondrial barrier.Nat Rev Mol Cell Biol. 2001;2:63-67.
71. Lazebnik YA,Kaufmann SH,Desnoyers S,Poirier GG,Earnshaw WC. Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature. 1994;371:346-347.
72. Juin P, Geneste O, Raimbaud E, Hickman JA. Shooting at survivors:Bcl-2 family members as drug targets for cancer. Biochim Biophys Acta.2004; 1644:251-260.
73.Reed JC, Pellecchia M. Apoptosis-based therapies for hematologic malignancies. Blood. 2005;106:408-418.
74.Zimmermann KC, Bonzon C,Green DR.The machinery of programmed cell death. Pharmacol Ther.2001;92:57-70.
75. Ranger AM, Zha J, Harada H,et al. Bad-deficient mice develop diffuse large B cell lymphoma. Proc Natl Acad Sci USA.2003;100:9324-9329.
76.Wang JL, Liu D, Zhang ZJ, et al. Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells.Proc Natl Acad Sci USA. 2000;97:7124-7129.
77.Carpten JD, Faber AL, Horn C, et al. A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature.2007;448:439-444.
78.Chen QC, Lee J, Jin W, et al., Cytotoxic constituents from angelicae sinensis radix. Arch Pharm Res.2007;30:565-569.
79.Rychahou PG, Jackson LN, Silva SR,et al.Targeted molecular therapy of the PI3K pathway: therapeutic significance of PI3Ksubunit targeting in colorectal carcinoma. Ann Surg.2006; 243: 833-842;discussion 843-844.
80.Wang J, Kuropatwinski K, Hauser J,et al.Colon carcinoma cells harboring PIK3CA mutations display resistance to growth factor deprivation induced apoptosis. Mol Cancer Ther. 2007; 6:1143-1150.
81.Liu Y, Chen L, Ko TC, et al.Evil is a survival factor which conveys resistance to both TGFbeta-and taxol-mediated cell death via PI3K/AKT. Oncogene.2006; 25:3565-3575.
82.Roulin D, Cerantola Y, Dormond-Meuwly A, et al.Targeting mTORC2 inhibits colon cancer cell proliferation in vitro and tumor formation in vivo. Mol Cancer.2010; 9:57.
83.Mikami I, Zhang F, Hirata T, et al.Inhibition of activated phosphatidylinositol 3-kinase/AKT pathway in malignant pleural mesothelioma leads to G1 cell cycle arrest. Oncol Rep.2010; 24: 1677-1681.
84.Dituri F, Mazzocca A, Lupo L, et al.,PI3K class IB controls the cell cycle checkpoint promoting cellproliferation in hepatocellular carcinoma. Int J Cancer.2012;130:2505-2513.
85.Brown RE, Tan D, Taylor JS, et al.Morphoproteomic confirmation of constitutively activated mTOR, ERK, and NF-kappaB pathways in high risk neuro-blastoma, with cell cycle andprotein analyte correlates. Ann Clin Lab Sci.2007;37:141-147.
86.Gao N, Zhang Z, Jiang BH,et al. Role of PI3K/AKT/mTOR signaling in the cell cycle progression of human prostate cancer. Biochem Biophys Res Commun.2003; 310:1124-1132.
87.Gao N, Flynn DC, Zhang Z, et al., G1 cell cycle progression and the expression of G1 cyclins are regulated byPI3K/AKT/mTOR/p70S6K1 signaling in human ovarian cancer cells. Am JPhysiol Cell Physiol.2004;287:C281-91.
88.Feng W, Duan X, Liu J, et al.Morphoproteomic evidence of constitutively activated and overexpressed mTOR pathway in cervical squamous carcinoma and high grade squamous intraepithelial lesions. Int J Clin Exp Pathol.2009;2:249-260.
89.Carpten JD, Faber AL, Horn C, et al.,A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature.2007;448:439-444.
90.Brown RE, Zhang PL, Lun M, et al. Morphoproteomic and pharmacoproteomic rationale for mTOR effectors as therapeutic targets in head and neck squamous cell carcinoma. Ann Clin Lab Sci.2006; 36:273-282.
91.Cardone MH, Roy N, Stennicke HR, et al. Regulation of cell death protease caspase-9 by phosphorylation. Science.1998;282:1318-1321.
92.Martinou JC,Green DR.Breaking the mitochondrial barrier. Nat Rev Mol Cell Biol.2001; 2: 63-67.
93.Lazebnik YA, Kaufmann SH, Desnoyers S,et al. Cleavage of poly (ADP-ribose) polymerase by a proteinase with properties like ICE. Nature.1994; 371:346-347.
1许瑞安,陈凌,肖卫东.分子基因药物学.北京大学医学出版社.2008：526-565.
2徐霞飞,陆茵.中药抗肿瘤血管生成研究进展.现代中药研究与实践.2007；21(1)：61-64.
3张芷旋,周清华.中药抗肺癌血管生成药物的研究进展.中国肺癌杂志.2006；9(1)：96-99.
4 Hurwitz HI, Fehrenbacher L, Hainsworth JD, et al. Bevacizumab in combination with fluorouracil and leucovorin:an active regimen for first line metastatic colorectal cancer. J Clin Oncol.2005;23:3502-3508.
5Kabbinavar FF, Hambleton J, Mass RD, et al. Combined analysis of eficacy:the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol.2005;23:3706-3712.
6 Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med.2004;350:2335-2342.
7 Saltz LB, Clarke S, Diaz-Rubio E, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer:a randomized phase III study.J Clin Oncol.2008;26:2013-2039.
8 Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med,2006,355:2542-2550.
9 Gilbert R, Wang M, Aldape K,etal. RTOG 0625:A phase Ⅱ study of bevacizumab with irinotecan in recurrent glioblastoma (GBM).2009 ASCO Annual Meeting, Abstract No:2001. [http://www.asco.org/, RTOG 0625]
lORini BI, Halabi S, Rosenberg JE,et al.Bevacizumab plus interferon-alpha versus interferon-alpha monotherapy in patients with metastatic renal cell carcinoma:Results of overall survival for CALGB 90206. J Clin Oncol.2010;13 (28):2137-2143.
11 Garcia AA, Hirte H, Fleming G,et al. Phase Ⅱ Clinical Trial of Bevacizumab and Low-Dose Metronomic Oral Cyclophosphamide in Recurrent Ovarian Cancer:A Trial of the California, Chicago, and Princess Margaret Hospital Phase Ⅱ Consortia.J Clin Oncol.2008;26(1):76-82.
12庄洪军,张全安,赵伟.血管内皮生长因子及其受体与肝癌治疗的研究进展.肿瘤研究与临床.2008；6：1618-1621.
13何立丽,苏航,张伟京,等.血管内皮细胞生长因子与抗肿瘤转移治疗的研究.国外医学药学分册.2006；33：2118-2121.
14何振辉,梁念慈.以VEGF和bFGF及其受体为靶点的抗肿瘤血管治疗.国外医学生理病理科学与临床分册.2004；24：162-166.
15张前,牛欣,闫妍,等.羟基红花黄色素A抑制新生血管形成的机制研究.北京中医药大学学报.2004；27(3)：25-29.
16徐晓玉,严鹏科,陈刚,等.川芎嗪对小鼠肺癌血管生长和VEGF表达的抑制.中国药理学通报.2004；20(2)：151-156.
17崔国惠,陈卫华,陈燕.姜黄素和肿瘤坏死因子α调节淋巴瘤细胞VEGF的表达及抗血管形成的研究[J].中国医院药学杂志.2008；28(22)：1918-1922.
18辛颖,倪劲松,王心蕊,等.20(S)-人参皂苷Rg3抗B16黑色素瘤转移的作用.吉林大学学报医学版.2004；30(4)：540-542.
19,张丰华,黄秀深,张萍.小柴胡汤对HL-60白血病细胞株体外分化的诱导作用研究.时珍国医国药.2009；(10).2657-2658
20韩燕,刘经选.天龙合剂对小鼠人胃癌细胞肿瘤生长及肿瘤血管生成的抑制作用.河北中医.2008；(8).874-876
21 ZhangL, Han Y, Wu F, et al. Expression and Clinical Significance of CD44 V6 and MVD in Human Colorectal Carcinoma.Practical Journal of Cancer.2004; 19(5):485-487.
22 Raspollini MR,Amunni G,Villanucci A,et al. Prognostic significance of micro vessel density and vascular endothelial growth factor expression in advcanced serous carcinoma. Int J Gynecol Cancer.2004; 14(5):815-823.
23 Maggi E, Parronchi P, Manetti R, et al. Reciprocal regulatory effects of IFN-gamma and IL-4 on the in vitro development of human Thl andTh2 clones.J Immunol.1992; 148 (7):2142-2147.
24 Jarnicki AG, Lysaght J, Todryk S, et al. Suppression of antitumor immunity by IL-10 and TGF-beta-producing T cells infiltrating the growing tumor:influence of tumor environment on the induction ofCD4+and CD8+regulatoryT cells J Immunol.2006; 177(2):896-904.
25 JonuleitH, SchmittE. The regulatory T cell family:Distinct subsets and their interrelations.J Immunol.2003;171(12):6323-6327.
26 Steinbrink K, Graulich E, Kubsch S, et al.CD4(+)and CD8(+) anergic T cells induced by interleukin-10-treated human dendritic cells display antigen-specific suppressor activity. Blood. 2002;99(7):2468-2476.
27 KishimotoT. Interleukin-6:from basic science tomedicine:40 years in immunology. Annu Rev Immunol.2005;23:1-21.
28 Hodge DR, HurtEM, FarrarWL. The role of IL6 and STAT3 in inflammation and cancer. Eur J Cancer.2005;41:2502-2512.
29 TchirkovA, KhalilT, Chautard E,et al. Interleukin-6 gene amplifi-cation and shortened survival in glioblastoma patients. Br J Cancer.2007;96:474-476.
30 Heriuchi Y,Hanazawa A,Nakajima Y,et al. T-helper Th1, Th2 imbalance in the peripheral blood of dog with malignant tumor.Microbiol Immunol.2007;51:1135-1138.
31 Sakaguchi E,Kayano K,Segawa M. Th1/Th2 imbalance in HCV-related liver cirrhosis. Nippon Rinsho.2001;59 (7):1259-1263.
32叶欣,李毅,刘忠民,等.大肠癌患者血清IL-10水平测定及其意义.肿瘤研究与临床.2002；14：171-173.
33 IndrovaM, BieblovaJ, Bubenik J, et al.IL-12 immunotherapy of minimal residual disease inmurinemodels of HPV16-associated tumours:induction of immune responses, cytokine production and kinetics of immune cell subsets.Int J Oncol.2008;32(2):499-507.
34 CarpentierAF. Cancer immunotherapy with Cp G-ODN.Med Sci (Paris),2005,21 (73):77.
35 Wu Y, Wan T, Zhou X, et al. Hsp70-like protein 1 fusion protein enhances induction of carcinoembryonic antigen-specific CD8+CTL response by dendritic cell vaccine. CancerRes. 2005;65:4947-4954.
36朱世杰,于莉莉,贾立群,等.参芪扶正注射液对荷瘤动物生存期影响的免疫机制研究.中华肿瘤防治杂志.2009；16(4)：264-266.
37丁治国,史晓光,汪唐顺,等.流式微球技术检测参芪扶正注射液对化疗小鼠Th1/Th2平衡状态的影响.中国实验方剂学杂志.2009；15(5)：39-41.
38伍杨,邓明会.长叶胡颓子对荷瘤鼠细胞免疫功能影响.中国公共卫生.2010；26(5)：576-577.