榄香烯注射液联合紫杉醇对宫颈癌和卵巢癌细胞生长抑制作用的研究
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摘要
目的：研究中药榄香烯联合紫杉醇对人宫颈癌细胞和人卵巢癌细胞生长的抑制作用。
方法：榄香烯注射剂联合紫杉醇分别与HeLa人宫颈癌细胞和H0-8910人卵巢癌细胞共培养48hr,用MTT分析法测定肿瘤细胞存活率,绘制药物浓度-存活曲线；取曲线中呈对数变化的药物浓度区间,以浓度和存活率(平均值±SD)对应的两个变量,求出对数回归方程,并计算出IC50。以IC50tax.comb对IC50tax.alone的比值,测定联合药物指数(Combination Index, CI),以此评价榄香烯对紫杉醇的增敏作用；CI≥1,表示无增敏作用,CI<1,表示有协同作用。同一种药物对不同细胞株的IC50差异采用单因素方差分析及t检验,若P<0.05表示有统计学意义。
结果：榄香烯注射剂和紫杉醇分别对HeLa和H0-8910细胞生长均有明显的抑制作用,随药物浓度的增加,其存活率随之降低,且呈药物浓度依赖关系,其IC50S EL.alone分别为43.74±3.51μg/ml、30.45±3.11μg/ml; IC50s Tax.alone分别为>100μmol／L和39.68±7.16μmol/L;榄香烯(IC10)联合紫杉醇分别作用HeLa和H0-8910细胞,其IC50S Tax.comb分别为52.75±4.20μmol/L和33.06±1.98μmol/L; ClTax.comb/Tax.alone分别为<0.53和0.83。结果显示,榄香烯注射剂对H0-8910细胞的抑制作用略强于对HeLa细胞(P<0.05)；而紫杉醇对H0-8910细胞的抑制作用显著强于对HeLa细胞(P<0.01),说明HeLa细胞对紫杉醇极不敏感或耐受；但榄香烯使紫杉醇对HeLa和H0-8910细胞的敏感性却分别增加了47.25%以上和24.4%,说明榄香烯联合紫杉醇对宫颈癌较卵巢癌细胞的细胞毒作用更高。
结论：榄香烯显著增加了紫杉醇对HeLa和H0-8910细胞诱导的细胞毒作用,尤其是对紫杉醇不敏感的HeLa细胞；联合榄香烯和紫杉醇获得的协同效应与由于榄香烯的作用而增强了紫杉醇细胞毒效应相关；榄香烯和紫杉醇的细胞毒作用存在明显差异,提示二者联合应用可能会更适宜于临床。
Objective:To explore potentially useful combinations of Elemenes injection with taxol in HeLa human cervical carcinoma cells and HO-8910PM human ovarian carcinoma cells.
Methods:HeLa cells and H08910PM cells were co-cultured with Elemenes combining with taxol respectively for 48 hours, and the growth inhibitions were determined by using MTT assay, the IC50's and Combination Index (IC50Tax.comb/IC50Tax.alone) were calculated as a curvilinear regression equation.
Results:Elemenes showed dose-dependent inhibition of HeLa cells and HO-8910 cells survival, but taxol showed inhibition only in HO-8910 cells not in HeLa cells. The IC50 values of elemenes and taxol for HO-8910 cells were 30.45±3.11μg. ml-1and 39.68±7.16μmol/L, respectively;for HeLa cells,43.74±3.51μg. ml-1 and>100μmol/L, respectively; the IC50 values of elemenes (IC10) combining with taxol for HO-8910 cells and HeLa cells were 33.06±1.98μmol/L and 52.75±4.20μmol/L, respectively. CITax/EL.comb/Tax.alone for HO-8910 cells and HeLa cells were 0.83 and≤0.53, respectively. Our findings showed that the inhibitory effects of Elemenes on the growth of HO-8910 cells were more significant than on HeLa cells growth(P<0.05); but the inhibitory effect of taxol on HO-8910 cells growth was much stronger than on HeLa cells growth (P<0.01), indicating extreme insensitivity or resistance of taxol to HeLa cells, and also showed that elemenes increased the sensitivity of taxol to HO-8910 cells and HeLa cells by 20.48% and 88.68% respectively, suggesting the enhanced cytotoxicity of elemenes in combination with taxol to HeLa cells more than to HO-8910 cells. Conclusion:Elemenes could inhibit the growth of HeLa and H08910PM cells, and significantly enhanced taxol-induced cytotoxicity to HeLa cells and H08910PM cells. The elemenes-induced alteration of cell membrane permeability, which has potential to result in enhanced cytotoxicity of taxol, may contribute to the synergistic interactions of the combination treatments in human cervical carcinoma cells and human ovarian carcinoma cells.
方法：榄香烯注射剂联合紫杉醇分别与HeLa人宫颈癌细胞和H0-8910人卵巢癌细胞共培养48hr,用MTT分析法测定肿瘤细胞存活率,绘制药物浓度-存活曲线；取曲线中呈对数变化的药物浓度区间,以浓度和存活率(平均值±SD)对应的两个变量,求出对数回归方程,并计算出IC50。以IC50tax.comb对IC50tax.alone的比值,测定联合药物指数(Combination Index, CI),以此评价榄香烯对紫杉醇的增敏作用；CI≥1,表示无增敏作用,CI<1,表示有协同作用。同一种药物对不同细胞株的IC50差异采用单因素方差分析及t检验,若P<0.05表示有统计学意义。
结果：榄香烯注射剂和紫杉醇分别对HeLa和H0-8910细胞生长均有明显的抑制作用,随药物浓度的增加,其存活率随之降低,且呈药物浓度依赖关系,其IC50S EL.alone分别为43.74±3.51μg/ml、30.45±3.11μg/ml; IC50s Tax.alone分别为>100μmol／L和39.68±7.16μmol/L;榄香烯(IC10)联合紫杉醇分别作用HeLa和H0-8910细胞,其IC50S Tax.comb分别为52.75±4.20μmol/L和33.06±1.98μmol/L; ClTax.comb/Tax.alone分别为<0.53和0.83。结果显示,榄香烯注射剂对H0-8910细胞的抑制作用略强于对HeLa细胞(P<0.05)；而紫杉醇对H0-8910细胞的抑制作用显著强于对HeLa细胞(P<0.01),说明HeLa细胞对紫杉醇极不敏感或耐受；但榄香烯使紫杉醇对HeLa和H0-8910细胞的敏感性却分别增加了47.25%以上和24.4%,说明榄香烯联合紫杉醇对宫颈癌较卵巢癌细胞的细胞毒作用更高。
结论：榄香烯显著增加了紫杉醇对HeLa和H0-8910细胞诱导的细胞毒作用,尤其是对紫杉醇不敏感的HeLa细胞；联合榄香烯和紫杉醇获得的协同效应与由于榄香烯的作用而增强了紫杉醇细胞毒效应相关；榄香烯和紫杉醇的细胞毒作用存在明显差异,提示二者联合应用可能会更适宜于临床。
Objective:To explore potentially useful combinations of Elemenes injection with taxol in HeLa human cervical carcinoma cells and HO-8910PM human ovarian carcinoma cells.
Methods:HeLa cells and H08910PM cells were co-cultured with Elemenes combining with taxol respectively for 48 hours, and the growth inhibitions were determined by using MTT assay, the IC50's and Combination Index (IC50Tax.comb/IC50Tax.alone) were calculated as a curvilinear regression equation.
Results:Elemenes showed dose-dependent inhibition of HeLa cells and HO-8910 cells survival, but taxol showed inhibition only in HO-8910 cells not in HeLa cells. The IC50 values of elemenes and taxol for HO-8910 cells were 30.45±3.11μg. ml-1and 39.68±7.16μmol/L, respectively;for HeLa cells,43.74±3.51μg. ml-1 and>100μmol/L, respectively; the IC50 values of elemenes (IC10) combining with taxol for HO-8910 cells and HeLa cells were 33.06±1.98μmol/L and 52.75±4.20μmol/L, respectively. CITax/EL.comb/Tax.alone for HO-8910 cells and HeLa cells were 0.83 and≤0.53, respectively. Our findings showed that the inhibitory effects of Elemenes on the growth of HO-8910 cells were more significant than on HeLa cells growth(P<0.05); but the inhibitory effect of taxol on HO-8910 cells growth was much stronger than on HeLa cells growth (P<0.01), indicating extreme insensitivity or resistance of taxol to HeLa cells, and also showed that elemenes increased the sensitivity of taxol to HO-8910 cells and HeLa cells by 20.48% and 88.68% respectively, suggesting the enhanced cytotoxicity of elemenes in combination with taxol to HeLa cells more than to HO-8910 cells. Conclusion:Elemenes could inhibit the growth of HeLa and H08910PM cells, and significantly enhanced taxol-induced cytotoxicity to HeLa cells and H08910PM cells. The elemenes-induced alteration of cell membrane permeability, which has potential to result in enhanced cytotoxicity of taxol, may contribute to the synergistic interactions of the combination treatments in human cervical carcinoma cells and human ovarian carcinoma cells.
引文
[1]Jeng-Leun Mau, Eric Y. C, lai, Nai-Phon Wang, Chien-Chou Chen, Chi-Huamg Chang, Charmg-Cherng Chyau. Composition and Antioxidant Activity of the Essential Oil From Curcuma Zedoaria. Food Chemistry,2003 (82):583-591
[2]彭炳先,周欣,王道平,等.HPLC法测定姜黄、莪术、郁金中三种姜黄色素的含量[J].中药材,2004,27(11)：813——815.
[3]崔晶,翟光喜,娄红祥.姜黄素的研究进展[J].中南药学,2005,3(2)：108-111.
[4]许刚,黄文.姜黄素防治肿瘤的机制研究进展[J].国外医学·生理、病理科学与临床分册,2003,23(2)：152～154.
[5]王琰,胡文言,王慕邹.HPLC法测定中药莪术中3种姜黄素的含量[J].药学学报,1999,34(6)：467-470.
[6]Ghaisas S D. Invitro studies on chemoprotective efect of purmark against benzo(a)pyrene-induced chromosomaldamagein human lymphocytes[J].Cell Biol Inter,1994,18(1):1085-1088.
[7]李侠,宋其林等,姜黄素抗突变作用的研究[J]卫生研究。1998,27(4)263-264
[8]Azuine M A, Kayal J. Protective role of aqueous turmeric extract against mutagenicity of directacting car cinogens asw ella s B(a)P yrene-induced genotoxicity and careinogenicity[J]Cancer Res Clin Oncol,1990,11(5):417-421.
[9]Oda-Y. Inhibitory effect of curcumin on SOS functions induced by UV Irradiation[J].Mutat Re s,1995,348:(2)67-69.
[10]Parshad R, Sanford K K, Price FM, etal. Protective action of plant polyphenols on radiation-induced chromatid breaks in cultured human cells [J]. AnticancerR es,1998,18(5):3263-3266
[11]张立实,张建清,王怡净.用TK墓因突变试验评价姜黄素的抗诱变性[J].癌变·畸变,突变.1999,11(6)：39-40.
[12]Mulky N. Clinicaldevelopment plan:Curcumin. India Drug,1987,25(3):72-85.
[13]NagabhushanM, Bhide SV. Nonmutagenicity of curcumin and its antimutagenic action versus chili and capsaicin [J]. NutrCancer,1 986,8(3):201-210
[14]Kuttan R, Bhanumathy P, Nirmala K, etal. Potential anticancer activity of turmeric (Curcumalonga) [J]. CancerLetter,1985,29(2):197-199.
[15]许建华,赵蓉,柯丹如.姜黄素的体外抗癌作用及其水溶液的稳定性[J].中国药理学通报,1998,14(5)：415-418.
[16]陈宏,张振书,张亚历,等姜黄素诱导Lov。细胞凋亡[J].中国中医墓础医学杂志.1999,5(3)：33-35.
[17]Mou TH, YouR L., Wei M, etal. Inhibitory etfect of dietary curcumin on forestomach, duodenal and colon carcinogenesis in mice[J]. Cancer Res,1994,54:5841-5847
[18]崔淑香,金东庆,周玲等.姜黄素抗肿瘤作用试验观察[P]肿瘤防治杂志.2002,9(1)：50-52.
[19]中华人民共和国药典委员会编.中华人民共和国药典[M]一部.北京：化学工业出版社,2000.218-235.
[20]Azuine M A, KayalJ. Protectiver orle of aqueous turmeric extract against mutagenicity of directacting carcinogens as well as B(a)Pyrene-induced genotoxicity and carcinogenicity[J]. Cancer Res Clin Oncol,1992,118(6):447-452.
[21]Pareira MA, GrubbsCJ, BamesLH, etal. Effects of thephyto chemicals, curcumin and quercetin, upon azo xy me thanein ducedc olonc anceran d7,12-dimethyl benz [a]anthracene induced mammary cancer in rats [J] Cacinogtnesis,1996,17:135-138.
[22]Huang MT, Smart RC, Wong C Q, etal. Inhibitory effect of curcumin, chlorogenic acid, caffeic acid and ferulic acid on tumor promotion in mouse skin byl2-0-tetradecanoylphorbol-13-acetate[J]. Cancerres,1988,48(21) :5841-5864.
[23]Menon L G,Kuttan G. Inhibition of lung metastasis in mice induced by B16f10 melanoma cells by polyphenolic compounds[J]. Cance L ett,1995,95 (122):221-225.
[24]李宁,陈晓欣,韩驰等.茶和姜黄素对二甲基苯并蒽诱发鼠口腔癌的预防作用[J].卫生研究,2002,31(5)：24-27.
[25]张建清,张立实,王瑞淑.姜黄素对TK6细胞的增殖抑制和凋亡诱导作用研究[J].营养学报,2003,25(3)：49-52.
[26]Ushida J, Sugie S, Kawahata K, etal. Chemopreventive effect.of curcumin on N-nitrosomethy Ibenzylamine induced esophageal carcino-genesis in rats[J] Jpn J Cancer Res,2000,91(9):
[27]Devasena T, Rajasekaran K N, Gunasekaran G et al. Anticarcinogenic effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione a curcumin analogo n DMH-induced colon cancer model[J].Pharmacol Res, 2003,47 (2):133.
[28]Shatini VK and leela Srinivas. Lipid Peroxide induced DNA damage:protection by turmeric(curcumalonga)[J]. Molecular and Cellular Biochemistry,1987,7(7):3-7.
[29]Ruby AJ, Kuttan G, Babu KD, etal. Antitumor and antioxidant activity of nutural curcuminoids[J]. Cancer Letters,1995:94(1):79-83
[30]Stano J, Grancai D, Neubert K, etal. Curcumin as a potential antioxidant[J].Ceska Slov Farm,2000,49(4):168-170.
[31]Phan T T, See P, Lee S T, et al. Protective efects of cucumin aginst oxidative damage on skin cells invit ro:itsi mplicalionf orw oundh ealing. JT rauma,2001,51 (4):927-931.
[32]Stano J, Grancai D,Neubert K, et al. Curcumin as a potential antioxidant[J]. Ceska Slov Farm,2000,49 (4):168-170.
[33]MouTH, YouRL, WeiM, etal. Inhibitoryefectofdietarycurcuminonforest
omach, duodenal and colon carcinoge nesisinmice[J], CancerRes,1994,54:5841-5847
[34]SoniK B, LahiriM, ChackradeF etal. Proteetive effect of food.additives on aflatoxin-induced mutagenicity and hepatocarcinogenicity [J].Cancer Lett,1997,115:129-3
[35]Thapliyal R, Deshpande S S, MaruG B. Efects of turmeric on the activities of benzo(a)pyrene-induced cytochrome. P-450 isozymes[JI. J Environ Pathol Toxicol Oncol,2001,20(1):59-63
[36]Thapliya IR, Deshpande S S, Maru G B Mechanism(s) of turmeric-mediated protective effects against benzo(a)pyrene-derived DNA adducts[J]. Cancer Lett,2002,175(1);79-82
[37]金莉,杨世勇姜黄素的研究进展[J]国外医学中医分册,1997,19(3)：49-50.
[38]Soudamini KK, Kutan R. Antitumor, bactericidal properties of curcumin[J].Amla Res Bull,1986,6:40-45
[39]Sindhwani, P. Hampton, Handjames, A:Curcumin prevents in travesical tumor inplantion of the MBT tumor cell line in C3H. mice[J]. Jurol,2001,166(4),1498-1501.
[40]周剑锋,李崇渔,陈燕细胞周期与肿瘤[J].国外医学输血及血液学分册,1996.19：40-43.
[41]许建华,赵蓉,柯丹如,等.姜黄素对人肝癌BEL-7402细胞杀伤动力学及周期时相的影响[J].福建医科大学学报,1998,32(3)：236-239
[42]Jaiswal AS, Marlow BP, Cupta N, et al. Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptoss in colon cancer cells[J]. Oncogene,2002,21(55):84-91.
[43]Moragoda L, Jaszewski R,Majumdar A P. Curcumin induced modulation of cell cycle and apoptosis in gastric and colon cancer cells[J]. Anticancer Res,2001,21 (2A):873-876.
[44]Conney A H, LouY R, Xie J G etal. Some perspectives on dietary
inhibition of carcinogenesis:studies with Curcumin and tea[J]. Proc Soc Exp Biol Med,1997,216:234-237.
[45]Liu Y, Chang R L Cui X X, etal. Differetiation in human promyelocytic leukemic HL-60 cell [J]s. Oncol Res,1997,9:19-29.
[46]Jiang M C, Yang Yen H F, Yen J J, etal. Curcumin induces apoptosis immortalized NIH3T3 and malignant cancer cell lines[J].Nutr Cancer,1998,19(4):611-616.
[47]Kuo M L, Huang TS, Lin JK.Biochim BiophyActa[M],1996,1317(2):95-100.
[48]Sikora E, Bielak Zmijewska A, Piwocka K, etal. Inhibition of proliferation and apoptosis of human and rat T lymphocytes by curcumin, a curry pigment[J]. Biochem Pharmacol,1997,54(8):899-907.
[49]Samaha HS, Kelloff GJ, SteeleV etal Modulation of apoptosis by sulindac, curcumin, phenylethyl-3-methylcafeate, and6-phenylhexyl is othiocyanate:apoptotic index as a biomarker in colon cancer
chemoprevention and promotion[J]. Cancer Res,1997,57:1301-1305.
[50]Anto RJ, Mukhopadhyay A, Denning K, etal. Curcumin(diferuloylme-thane) induces apoptosis through act ivation of caspase-8, BID cleavage and cytochromec release:its suppression by ectopic expression of Bcl-2 and Bcl-xl [J]Carcinogenesis,2002,23(1):143-146.
[51]Kim M S, Kang HJ, Moon A. Inhibition of invasion and induction of apoptosis by curcumin in H-ras-transformed MCFIOA human breast epithelial cells[J]. Arch Pharm Res,2001,24(4):349.
[52]Choudhuri T, Pal S, Agwarwal M L, etal Curcumin induces apoptosis in human breast cancer cells through p53 dependent Bax induction[J].FEESL et,2002,512(123):334-338.
[53]Kakar S S, Roy D. Curcum in inhibits TPA induced expression of c-fos, c-Jun and c-myc proto-oncogenes messenger RNAs in mouse skin[J]. Cancer Lett,1994,87(1):85-88
[54]Bush J A, Cheung KJ Jr, Li G. Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8pathway independent of p53[J].Exp Cell Res,2001,271(2):305-314.
[55]Lin LI, Ke Y F, Ko YC. Curcumin inhibits SK-Hep-Ihep-atocellular carcinoma cell invasion in vitro and suppressesm atrixmetall proteinase-9secretion [J]. Oncology,1998,55(4):349-353.
[56]Arbiser J L, Klauber N, Rohan R, etal. Curcumin is an in vitro inhibitor of angiogenesis [J].Mol Me d,1998,4(6):376-383.
[57]高承贤,丁志山,梁冰冰等.姜黄素对血管生成影响的实验研究[J].中药材2003,26(7)：499-502.
[58]Aggarwal B B, Kumar A, BhartiA C. Anticancer potential of curcumin; preclinical and linical studies[J]. Anticancer Res.2003,23 (IA):363-366.
[59]ZhengS, Yang H, Zhang S, et al. Intial study on naturally occurring products from traditional Chinese herbs and vegetables for chemoprevention. J Cell Biochem Suppl,1997;27:106--12
[60]杨骅,王仙平,郁琳琳.榄香烯抗癌作用与诱发肿瘤细胞凋亡.中华肿瘤杂志,1996,18(3)：169-172
[61]范钰,林庚金,钱立平,等.榄香烯乳对胃癌SGC-7091细胞株端粒酶活性及细胞凋亡的影响.复旦学报(医学科学版),2001,28(1)：5-8
[62]傅乃武,全兰萍,郭永,等β-榄香烯的抗肿瘤作用和药理学研究.中药1984：9(2)：35-9
[63]秦叔选,钱军,杨爱珍,等.β-榄香烯乳抗肺癌细胞的实验研究.肿瘤防治研究,1996：23(4)：251--5
[64]郝立宏,卢步峰,于丽敏,等.β-榄香烯与阿霉素联合应用对CEM/APM细胞生长的影响大连医科大学学报,2000,22(3)：12
[65]徐学军,周子成,罗元辉,等β-榄香烯诱导人肝癌细胞株SMMC-7721凋亡的研究.第三军医大学学报,1999,21(4)：268-271
[66]马东礼,童善庆.榄香烯对HeLa细胞端粒酶催化亚单位基因表达的作用.中
国癌症杂志2001,11(1)：9-13
[67]Hiyama K, Hiyama E, lshioka S, et al. Telomerase activity in small-cell and non-small-cell lung cancer ·J Natl Cancer Inst.1995,87(12):895-902.
[68]Kerr J FR, Wyllie AH, Currie AR. Apoptosis:a basic biological phenomenon with wide ranging implication in tissue kinetics. Br J Cancer,1972,26:239
[69]Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science,1995,267(5203):1456-1462
[70]Kasagi N, Somyo Y, S hirai H,et al.Al and cancer. J cancer Res.1994:85(9):939-945
[71]Fulvio B,Lisa F,Alfredo F, et a 1. Potentiation of the malignant phenotype of the differentiated ARO thyroid cell line by insertion of the bcl-2 gene. Int J cancer 1999,81:956-962
[72]Green DR. Apoptotic pathways:paper wraps stone blunts scissors. Cell,2000,102:1
[73]G reen DR, Reed Jc. Mitochondrion and apoptosls. Science,1 998,281 (28):1309
[74]Martinous Jc, Desagher S, Antonsson B. Cytochrome C release from mitochondria:all or nothing. Nature cell biology,2000,2:41
[75]Li K, Li Y, Shelton JM, et al. Cytochrome C, deficiency causes embryonic Lethality and attenuates stress-induced apoptosis. Cell,2000,10 1(4):398
[76]Ashkenazi A.Dixit VM. Death receptors:signaling and modulation. Science,1998,281(28):1305
[77]Hussein MR, Haemel AK, Wood GS. Apoptosis and melanoma:molecular mechanisms. Pathol,2003,199(3):275-288
[78]Konno R, Yamakawa H, Utsunomiya H, et al. Expression of suryivin and bcl-2 in the Normal human endometrium. Mol Hum Reprod,2000,6(6):529
[79]Am brosini G,Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med,1997, 3(8):917-921.
[80]Altieri DC, Marchisio PC, Marchisio C.Survivin apoptosis:an interloper Between cell death and cell proliferation in cancer. Lab Invest,1999,79 (11):1327-1333.
[81]Tamm I, WangY,Sausville E, et al. IAP-family protein surviving inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res,1998,58(23):5315-5320
[82]Suzuki A, Ito T, Kawano H, et al.Survivin initiates procaspase3/p21 complex formation as a result of interaction with CDK4 to resist Fas-mediated cell death. Oncogene,2000,19 (10):1346
[83]Oconnor DS, Schechner JS, Adida C, et al.Control of apoptosis during angiogenesis by survivin expressi n endothelial cell. Am J Pathol,2000,156 (2):393
[84]Papapetropoulos A, Fulton D, Mubboubi K, et al. Angiopioetin 1 inhibits Endothelial cell.J Biol Chem,2000,275(13):9102
[85]Hirokazu 0, Hitoshi T, Hideyasu 0, et al. Phos-phatidylinositol 3-Kinase/Akt regulates angiotensin 1I-in-duced inhibition of apoptosis in microvascular endothelial cells by governing survivin expression and suppression of caspase-3 activity circ. Res,2004, 94:785
[186]Kishi H, Igawa M, Kikuno N, et al. Expression of the survivin gene in prostate cancer:correlation with clinicopatho-logical characteristics, proliferative activity and apoptosis. J Urol, 2004,171(5):1855
[87]Kren L, Brazdil J, Hermanova M, et al. Prognostic significance of anti-apoptosis proteins surviving and bcl-2 in non-small cell lung carcinomas:a clinicopathologic study of 102 cases. Appl
Immunohistochem Mol Morphol,2004,12 (1):44
[88]Satoh K, Kaneko K, Hirota M, et al. Expression of survivin is correlated with cancer cell apoptosis and is involvedin the development of human pancreatic duct cell tumors. Cancer,2001,92 (2):271-278
[89]Lu CD,Altieri DC, Tanigawa N. Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastriccarcinomas. Cancer Res,1998, 58(9):1808-1812
[90]Adida C, Berrebi D, Peuchmaur M, et al. Anti-apoptosis gene, survivin, and prognoses of neuroblastoma. Lancet,1998, 351(9106):882-883
[91]汪小明,黄循,张选志.膀胱移行细胞癌中凋亡抑制因子survivin的表达及意义.中国现代医学杂志,2004,14(2)：25
[92]Andersen MH, Pedersen L0, Capeller B, et al. Spontaneous cyotoxic Tcell Responses against survivin-derived MHC class I-restricted T-cell epitopes in situ as well as exvivo in cancer patients. Cancer Res,2001,61(16):5964-5968
[93]Altieri DC. Validating survivin as a cancer therapeutic target. Nat Rev Cancer,2003,3(1):46
[94]Marzia P, Mara B, Michelandrea DC. Ribozyme-mediated down-regulation of survivin expression sensitizes human melanoma cells to topotecan in vitro and in vivo. Carcinogenesis,2004,10(5):1093
[95]Enari M. A casepase-activated Dnase that degrades DNA and its inhibitor ICAD during apoptosis. Nature,1998,391:43
[96]Reed JC. Mechanisms of Bcl-2 family protein function and dysfunction in health and disease.Behring Inst Mitt,1996,97:72-100
[97]Jacobson MD. Apoptosis:Bcl-2-related proteins get connected. Curr Biol,1997,7(5):R277-281
[98]Jerry M, Adams, Suzase Cory. Science,1998,281(5381):1322-1326
[99]Thombeny NA, Lazebnik Y. Caspase enemies within. Science,1998, 281(28):1312
[100]MuchmoreS W, Sattler M, Liang H, et al.X-ray and NMR structure of human Bcl-xl, an inhibitor of programmed cell death, Nature,1996,38 1(6580):335-341
[101]Minn AJ, Kettlun CS, Liang H et al. Bcl-xL regulateds apoptosis by heterodimerization-dependent and-independent mechanisms. EMBO J, 1999,18(3):632-643
[102]Shangary S, Johnson DE. Recent a vances in the development.of anticancer agents targeting cell death inhibitors in the Bcl-2. protein family. Leukemia,2003,17(8):1470-1481
[103]Biroccio A, Benassi B, D'Agnanol, et al. c-Myb and Bcl-xoverexpression predicts poor prognosis in colorectal cancer:clinical and experimental findings. AmJ Pathol,2001, 158(4):1289--1299
[104]HattoriT, OokawaN, Fujita R, et al. Heterodimerization of Bcl-2 and Bcl-X(L) With Bax and bad in colorectal cancer. Acta Oncol,2000,39 (4):495-500
[105]Olopade OI, Adeyan ju M0, Safa AR, et al. Overexpression of Bcl-x preotein In primary breast cancer is associated with high tumor grade and nodal metastases. Cancer J Sci Am,1997,3(4):230--237
[106]Zhang C1, Kamarashev J, Qin JZ, et al. Expression of apoptosis regulators in cutaneous T-cell lymphoma (CTCL) cells. J Pathol. 2003,200(2):249-254
[107]Frankel A,R osenK, Filmus J, etal. Induction of anoikis and suppression of human ovarian tumor growth in vivo by down-regulation of Bcl-X. Cancer Res,2001,61(12):4837-4841
[108]Gazzaniga, GradiloneA,S ilvestril,et al. Variable levels of bcl-2, bcl-x and bax mRNA in bladder cancer progression. Oncol Rep,1998,5(4):901-904
[109]Gazzaniga P, G radiloneA,G iuliani L et al. Expression and prognostic Significance of livin, survivin and other apoptosis-related genes in the progression of superficial bladder cancer. Ann Oncol,2003,14(1):85-90
[110]袁静,顾振伦.榄香烯诱导K562细胞凋亡的流式细胞术分析.实用肿瘤杂志,1998,(6)：343-344
[111]范钰,林庚金,钱立平等.榄香烯对胃癌SGC7901细胞bcl-2基因表达及端粒酶活性的影响.上海医学.2001,24(8)：490-492
[112]范钰,林庚金,钱立平等.榄香烯对胃癌SGC-7901细胞C-myc基因表达及端粒酶活性的影响.中国肿瘤临床,2001,28(11)：848-851
[113]刘宇男,.王国良,贾永峰,等.MTT法在榄香烯乳对人膀肌癌T24细胞体外实验中的应用.上海医科大学学报,1997,24(2)：127-130
[114]李传刚,刘用揖,冯秉安,等.0一榄香烯对人BIU-87细胞诱导凋亡的实验研究中国中西医结合外科杂志,1999,5(6)：387-390
[115]李传刚,李墨林,舒晓宏等.0一榄香烯对人膀耽癌BIU-87细胞磷脂代谢转换率及细胞脂膜流动性的影响.中华医学杂志,2004,84(5)：416-417
[116]钱军,秦叔遗,杨爱珍,等榄香烯乳逆转人肺癌细胞的实验研究.肿瘤防治研究,1996：23(5)：29 9-301
[117]吴伟忠,刘康达,汤晓雷,等.p一榄香烯诱导的抗肿瘤免疫保护作用机理初探.中华肿瘤杂志,1999,21(6)：405-408
[118]钱振超,刘金友,赵肃荣,等.获术瘤苗的主动免疫保护效应一羲术抗癌作用原理的探讨.药学学报,1981；16(12)：892-6
[119]金梅,施广霞,朴花,等.榄香烯复合瘤苗主动免疫的抗肿瘤效应.中国肿瘤防治杂志,1999,6(1)：50-51
[120]官成浓,何国章.榄香烯乳配合化疗对进展期胃癌患者免疫功能的影响中国肿瘤临床,2001,28(2)：123-124
[121]陈龙邦,藏静,王靖华.5一榄香烯对荷瘤小鼠免疫功能的影响.肿瘤防治
研究,1998,25(1)：54
[122]张学军,杜权,丁秀萍,等.榄香烯乳对r-DNA转录活性的影响及意义.中国肿瘤临床,1999,26(3)：443-444
[123]郦志军,周君富, 陈周苗,等.榄香烯对肺癌患者血液SOD活性和LPO浓度的影响研究.中国肿瘤临床,1998,25(11)：82 5-853
[124]陈龙邦,藏静,王靖华,等.s一榄香烯对小鼠B16黑色素瘤细胞粘附,运动和间隙连接通讯功能的影响.肿瘤防治研究,1999,26(3)：195-197
[125]颜大海,朱树林,李鑫,等.鸡胚法筛选具有血管生成抑制作用中药.黑龙江医药,1998,11(2)：94
[126]王宝成,郭军,狄剑时,等.榄香烯乳剂与肿瘤多药耐药的基础研究.中国肿瘤临床,1996：23(2)：143--6
[127]Toh Y, Pencil SD, Nicolson GL, A Novel cndidate metastasis associated gene, mtal, differentially expressed in high metastatic mammary adenocarcinom a cell line. J Biological Chemistry,1994;269(37):22958.
[128]Cui Q, Takiguchi S, Matsusue K, e t al.A ssignment of the human metastasis-associated gene 1 (MTA1) to human chromosome band 14q32.3 by fluorescence in situ hybridization. Cytogenet Cell Genet,2001, 93:139-140.
[129]Toh Y,O kiE, Oda S, et al. Overexpression of the mta 1 gene in gastrointestinal carcinomas:correlation with invasion and metastasis. Int J Cancer,1997,74:459-463.
[130]Nicolson GL, NawaA, Toh Y et al.Tumorm etastasis-associated human MTA1 gene and its MTA1 product:role in epithelial cancer cell invasion, proliferation and nuclearre gulation. Clin Exp Metastasis,2003,20 (1):19-24
[131]Toh Y, Kuninaka S, Endo K, et al. Molecular analysis of a candidate metastasis-associated, M TAl:possible inferaction with histone deacetylasel.J Exp Clin Cancer Res,2000;19(1):105
[132]杨磊,丁颜青.肿瘤转移相关基因Mta-1和肿瘤.医学综述2003,9(1)：24-25
[133]唐桥斐,季文越等.转移相关基因表达与喉鳞状细胞癌淋巴结转移的关系.中华耳鼻咽喉科杂志,2003,38(3)：213-216
[134]Matthias D, Rainer K, Sooryanarayana V, etal.The role of metastasis-associated protein 1 in prostate cancer progression. Cancer Research,2004,64:825-829
[135]Mahoney MQ Simpson A, JostM, et al.Metastasis-associatedp rotein(MTA)1 enhances migration, invasion, and anchorage-independent survival of immortalized human eratinocytes. Oncogene,2002,21(14):2161-70
[136]Folkman.J. Role of Angiogenesis in tumor growth and metastasis[J]. Semin Oncol,2002,29:15-18.
[137]Hashizume H, Baluk P, Morkawa S, et al. Openings between defective endothelial cells explain tumor vessel leakiness[J]. Am J Pathol,2000,156(4):1363-1380.
[138]陈文清.莪术油治疗小儿病毒性肺炎疗效观察.江西医学院学报,2004,44(2)：22
[139]王新生,王成芬,王利燕.莪术油葡萄糖注射液治疗病毒性肺炎的疗效观察.中医药研究,2000,16(3)：16,40
[140]徐明,薛业群,葛必胜.莪术油注射液治疗小儿急性支气管炎和肺炎.湖北中医杂志,2004,26(4)：19
[141]叶茂.莪术油葡萄糖注射液治疗婴幼儿间质性肺炎的疗效观察.儿科药学杂志,2004,10(4)：58-59
[142]方淑彩,唐瑜琦.莪术油佐治小儿支原体肺炎的疗效观察.齐齐哈尔医学院学报,2004,25(5)：5 32
[143]仇付丽.莪术油治疗毛细支气管炎122例.中医研究,2004,17(3)：30
[144]戴怡蕃,范联,吴燕玲.莪术油葡萄糖注射液治疗急性上呼吸道感染85例临床观察.广东药学院学报,2001,17(3)：225-227
[145]丛艳华,王双妹,王双红.莪术油治疗婴幼儿肺炎疗效观察.黑龙江医药科学,2001,24(1)：24
[146]王幼萍.莪术油治疗带状疙疹45例.医药导报,2004,23(12)：912-913
[147]焦建萍.莪术油葡萄糖注射液治疗麻疹40例疗效分析山东医药,2001,41(17)：72-73
[148]俞笑林.莪术油治疗婴幼儿病毒性肠炎312例.中国药业,2003,12(3)：68
[149]史玲艾,丁翠,杜静等.莪术油注射液治疗小儿病毒性心肌炎疗效观察.河北中医,2004；26(3)：2 26
[150]李正凡.莪术油葡萄糖注射液治疗小儿流行性腮腺炎42例.湖南中医杂志,2003,19(1)：47
[151]吴建敏.莪术油葡萄糖注射液治疗急性病毒性脑炎疗效观察.海峡药学,2003,15(1)：49-50
[152]袁超英,陈朝俊.莪术油注射液治疗病毒性结膜炎的临床观察.湖北中医杂志,2002,24(11)：34
[153]张辉,罗开国.莪术油滴眼液治疗单纯疙疹性病毒性角膜炎的临床观察.中国医院药学杂志2001,21(8)：489-490
[154]吴玉华,方建华.莪术油治疗病毒性风疹.中国基层医药,2002,9(10)：
[155]张小虎等。莪术油治疗宫颈癌2007,23(12)：912-913
[156]吴万垠,徐凯,刘伟胜等。莪术油微球经肝动脉灌注栓塞治疗原发性肝癌,上海中医药杂志,2004,38(4)：3-6
[157]李智勇,等晓军。莪术油等经植泵治疗姑息性切除术后晚期大肠癌的临床观察.中国中西医结合外科杂志,2002,8(5)：343-344
[158]魏兰福,邹百仓,魏睦新.莪术对实验性功能性消化不良大鼠胃排空的影响[J].南京医科大学学报,2003,23(4)：450-352.
[159]郑方周,李玉升.莪术油治疗小儿科季腹泻临床疗效观察[J].临圻医学专科学校学报,2003,25(3)：397-499
[160]周继红等.莪术油治疗三期褥疮的临床观察。浙江中医药大学学报2008年7月第32卷
[161]李卫彬,陈朝俊.莪术油治疗外感高热症113例临床观察.湖北中医
[J].2003；25(6)：20
[162]宋勉,马利军.清开灵胶囊配合莪术油葡萄糖注射液治疗高热110例[J].光明中医,2001；16(4)：42-43
[163]王培养.莪术油注射液治疗4,JL手足口病疗效观察[J].浙江中西医结合杂志,2003；13(7)：437
[164]沈美珍.莪术油加西瓜霜联合治疗婴幼儿手足口病临床观察[J].宁夏医学杂志。2003；25(2)：108
[165]龚湛潮。白波.莪术油葡萄糖注射液治疗咽结合膜热的疗效观察[J].四川医学,2003；24(8)：840
[166]许刚,李魏等.莪术油治疗皮肤溃疡的临床观察[J].广州中医药大学学报2006,23(5)115-116
[167]李路等.莪术油对皮肤放射损伤的临床观察[J]中国临床杂志.2007：22(3)123-125
[168]陈丽,高骅等。莪术油对甲型肝炎的临床观察[J]中西医结合杂志2008,12(3)113-135
[169]林光勇.莪术油药理作用及临床用药的研究进展[J].广东药学,2002,12(1)：12-14.
[170]李爱群,姚祟舜,许风,等.不同产地莪术挥发油的有效成分f-j].分析测试学报,2002,21(6)：67—69,
[171]Hisashi M. Inhibitory effect and action mechanism of sesquit-erpenes from zedoariae rhizoma on-galactosamine/lipopolysac-charid induced liver injury[J]. Bioorg Med Chem Lett,1998, 8(4):339-341.
[172]Yoshinori S, Tomoko I. Biomimetic transformation of dehydrocur-dione into curcumenol and isocurcumenol and their stereochemis-tries [J]. Tetrahedron Lett,1985,26(7):913-915.
[173]Navarro F, Souza MM. Phytochemical analysis and analgesicproperties of Curcuma zedoaria grown in Brazil [J]. Phytomedi-cine,2002,9(5): 427-428.
[2]彭炳先,周欣,王道平,等.HPLC法测定姜黄、莪术、郁金中三种姜黄色素的含量[J].中药材,2004,27(11)：813——815.
[3]崔晶,翟光喜,娄红祥.姜黄素的研究进展[J].中南药学,2005,3(2)：108-111.
[4]许刚,黄文.姜黄素防治肿瘤的机制研究进展[J].国外医学·生理、病理科学与临床分册,2003,23(2)：152～154.
[5]王琰,胡文言,王慕邹.HPLC法测定中药莪术中3种姜黄素的含量[J].药学学报,1999,34(6)：467-470.
[6]Ghaisas S D. Invitro studies on chemoprotective efect of purmark against benzo(a)pyrene-induced chromosomaldamagein human lymphocytes[J].Cell Biol Inter,1994,18(1):1085-1088.
[7]李侠,宋其林等,姜黄素抗突变作用的研究[J]卫生研究。1998,27(4)263-264
[8]Azuine M A, Kayal J. Protective role of aqueous turmeric extract against mutagenicity of directacting car cinogens asw ella s B(a)P yrene-induced genotoxicity and careinogenicity[J]Cancer Res Clin Oncol,1990,11(5):417-421.
[9]Oda-Y. Inhibitory effect of curcumin on SOS functions induced by UV Irradiation[J].Mutat Re s,1995,348:(2)67-69.
[10]Parshad R, Sanford K K, Price FM, etal. Protective action of plant polyphenols on radiation-induced chromatid breaks in cultured human cells [J]. AnticancerR es,1998,18(5):3263-3266
[11]张立实,张建清,王怡净.用TK墓因突变试验评价姜黄素的抗诱变性[J].癌变·畸变,突变.1999,11(6)：39-40.
[12]Mulky N. Clinicaldevelopment plan:Curcumin. India Drug,1987,25(3):72-85.
[13]NagabhushanM, Bhide SV. Nonmutagenicity of curcumin and its antimutagenic action versus chili and capsaicin [J]. NutrCancer,1 986,8(3):201-210
[14]Kuttan R, Bhanumathy P, Nirmala K, etal. Potential anticancer activity of turmeric (Curcumalonga) [J]. CancerLetter,1985,29(2):197-199.
[15]许建华,赵蓉,柯丹如.姜黄素的体外抗癌作用及其水溶液的稳定性[J].中国药理学通报,1998,14(5)：415-418.
[16]陈宏,张振书,张亚历,等姜黄素诱导Lov。细胞凋亡[J].中国中医墓础医学杂志.1999,5(3)：33-35.
[17]Mou TH, YouR L., Wei M, etal. Inhibitory etfect of dietary curcumin on forestomach, duodenal and colon carcinogenesis in mice[J]. Cancer Res,1994,54:5841-5847
[18]崔淑香,金东庆,周玲等.姜黄素抗肿瘤作用试验观察[P]肿瘤防治杂志.2002,9(1)：50-52.
[19]中华人民共和国药典委员会编.中华人民共和国药典[M]一部.北京：化学工业出版社,2000.218-235.
[20]Azuine M A, KayalJ. Protectiver orle of aqueous turmeric extract against mutagenicity of directacting carcinogens as well as B(a)Pyrene-induced genotoxicity and carcinogenicity[J]. Cancer Res Clin Oncol,1992,118(6):447-452.
[21]Pareira MA, GrubbsCJ, BamesLH, etal. Effects of thephyto chemicals, curcumin and quercetin, upon azo xy me thanein ducedc olonc anceran d7,12-dimethyl benz [a]anthracene induced mammary cancer in rats [J] Cacinogtnesis,1996,17:135-138.
[22]Huang MT, Smart RC, Wong C Q, etal. Inhibitory effect of curcumin, chlorogenic acid, caffeic acid and ferulic acid on tumor promotion in mouse skin byl2-0-tetradecanoylphorbol-13-acetate[J]. Cancerres,1988,48(21) :5841-5864.
[23]Menon L G,Kuttan G. Inhibition of lung metastasis in mice induced by B16f10 melanoma cells by polyphenolic compounds[J]. Cance L ett,1995,95 (122):221-225.
[24]李宁,陈晓欣,韩驰等.茶和姜黄素对二甲基苯并蒽诱发鼠口腔癌的预防作用[J].卫生研究,2002,31(5)：24-27.
[25]张建清,张立实,王瑞淑.姜黄素对TK6细胞的增殖抑制和凋亡诱导作用研究[J].营养学报,2003,25(3)：49-52.
[26]Ushida J, Sugie S, Kawahata K, etal. Chemopreventive effect.of curcumin on N-nitrosomethy Ibenzylamine induced esophageal carcino-genesis in rats[J] Jpn J Cancer Res,2000,91(9):
[27]Devasena T, Rajasekaran K N, Gunasekaran G et al. Anticarcinogenic effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione a curcumin analogo n DMH-induced colon cancer model[J].Pharmacol Res, 2003,47 (2):133.
[28]Shatini VK and leela Srinivas. Lipid Peroxide induced DNA damage:protection by turmeric(curcumalonga)[J]. Molecular and Cellular Biochemistry,1987,7(7):3-7.
[29]Ruby AJ, Kuttan G, Babu KD, etal. Antitumor and antioxidant activity of nutural curcuminoids[J]. Cancer Letters,1995:94(1):79-83
[30]Stano J, Grancai D, Neubert K, etal. Curcumin as a potential antioxidant[J].Ceska Slov Farm,2000,49(4):168-170.
[31]Phan T T, See P, Lee S T, et al. Protective efects of cucumin aginst oxidative damage on skin cells invit ro:itsi mplicalionf orw oundh ealing. JT rauma,2001,51 (4):927-931.
[32]Stano J, Grancai D,Neubert K, et al. Curcumin as a potential antioxidant[J]. Ceska Slov Farm,2000,49 (4):168-170.
[33]MouTH, YouRL, WeiM, etal. Inhibitoryefectofdietarycurcuminonforest
omach, duodenal and colon carcinoge nesisinmice[J], CancerRes,1994,54:5841-5847
[34]SoniK B, LahiriM, ChackradeF etal. Proteetive effect of food.additives on aflatoxin-induced mutagenicity and hepatocarcinogenicity [J].Cancer Lett,1997,115:129-3
[35]Thapliyal R, Deshpande S S, MaruG B. Efects of turmeric on the activities of benzo(a)pyrene-induced cytochrome. P-450 isozymes[JI. J Environ Pathol Toxicol Oncol,2001,20(1):59-63
[36]Thapliya IR, Deshpande S S, Maru G B Mechanism(s) of turmeric-mediated protective effects against benzo(a)pyrene-derived DNA adducts[J]. Cancer Lett,2002,175(1);79-82
[37]金莉,杨世勇姜黄素的研究进展[J]国外医学中医分册,1997,19(3)：49-50.
[38]Soudamini KK, Kutan R. Antitumor, bactericidal properties of curcumin[J].Amla Res Bull,1986,6:40-45
[39]Sindhwani, P. Hampton, Handjames, A:Curcumin prevents in travesical tumor inplantion of the MBT tumor cell line in C3H. mice[J]. Jurol,2001,166(4),1498-1501.
[40]周剑锋,李崇渔,陈燕细胞周期与肿瘤[J].国外医学输血及血液学分册,1996.19：40-43.
[41]许建华,赵蓉,柯丹如,等.姜黄素对人肝癌BEL-7402细胞杀伤动力学及周期时相的影响[J].福建医科大学学报,1998,32(3)：236-239
[42]Jaiswal AS, Marlow BP, Cupta N, et al. Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptoss in colon cancer cells[J]. Oncogene,2002,21(55):84-91.
[43]Moragoda L, Jaszewski R,Majumdar A P. Curcumin induced modulation of cell cycle and apoptosis in gastric and colon cancer cells[J]. Anticancer Res,2001,21 (2A):873-876.
[44]Conney A H, LouY R, Xie J G etal. Some perspectives on dietary
inhibition of carcinogenesis:studies with Curcumin and tea[J]. Proc Soc Exp Biol Med,1997,216:234-237.
[45]Liu Y, Chang R L Cui X X, etal. Differetiation in human promyelocytic leukemic HL-60 cell [J]s. Oncol Res,1997,9:19-29.
[46]Jiang M C, Yang Yen H F, Yen J J, etal. Curcumin induces apoptosis immortalized NIH3T3 and malignant cancer cell lines[J].Nutr Cancer,1998,19(4):611-616.
[47]Kuo M L, Huang TS, Lin JK.Biochim BiophyActa[M],1996,1317(2):95-100.
[48]Sikora E, Bielak Zmijewska A, Piwocka K, etal. Inhibition of proliferation and apoptosis of human and rat T lymphocytes by curcumin, a curry pigment[J]. Biochem Pharmacol,1997,54(8):899-907.
[49]Samaha HS, Kelloff GJ, SteeleV etal Modulation of apoptosis by sulindac, curcumin, phenylethyl-3-methylcafeate, and6-phenylhexyl is othiocyanate:apoptotic index as a biomarker in colon cancer
chemoprevention and promotion[J]. Cancer Res,1997,57:1301-1305.
[50]Anto RJ, Mukhopadhyay A, Denning K, etal. Curcumin(diferuloylme-thane) induces apoptosis through act ivation of caspase-8, BID cleavage and cytochromec release:its suppression by ectopic expression of Bcl-2 and Bcl-xl [J]Carcinogenesis,2002,23(1):143-146.
[51]Kim M S, Kang HJ, Moon A. Inhibition of invasion and induction of apoptosis by curcumin in H-ras-transformed MCFIOA human breast epithelial cells[J]. Arch Pharm Res,2001,24(4):349.
[52]Choudhuri T, Pal S, Agwarwal M L, etal Curcumin induces apoptosis in human breast cancer cells through p53 dependent Bax induction[J].FEESL et,2002,512(123):334-338.
[53]Kakar S S, Roy D. Curcum in inhibits TPA induced expression of c-fos, c-Jun and c-myc proto-oncogenes messenger RNAs in mouse skin[J]. Cancer Lett,1994,87(1):85-88
[54]Bush J A, Cheung KJ Jr, Li G. Curcumin induces apoptosis in human melanoma cells through a Fas receptor/caspase-8pathway independent of p53[J].Exp Cell Res,2001,271(2):305-314.
[55]Lin LI, Ke Y F, Ko YC. Curcumin inhibits SK-Hep-Ihep-atocellular carcinoma cell invasion in vitro and suppressesm atrixmetall proteinase-9secretion [J]. Oncology,1998,55(4):349-353.
[56]Arbiser J L, Klauber N, Rohan R, etal. Curcumin is an in vitro inhibitor of angiogenesis [J].Mol Me d,1998,4(6):376-383.
[57]高承贤,丁志山,梁冰冰等.姜黄素对血管生成影响的实验研究[J].中药材2003,26(7)：499-502.
[58]Aggarwal B B, Kumar A, BhartiA C. Anticancer potential of curcumin; preclinical and linical studies[J]. Anticancer Res.2003,23 (IA):363-366.
[59]ZhengS, Yang H, Zhang S, et al. Intial study on naturally occurring products from traditional Chinese herbs and vegetables for chemoprevention. J Cell Biochem Suppl,1997;27:106--12
[60]杨骅,王仙平,郁琳琳.榄香烯抗癌作用与诱发肿瘤细胞凋亡.中华肿瘤杂志,1996,18(3)：169-172
[61]范钰,林庚金,钱立平,等.榄香烯乳对胃癌SGC-7091细胞株端粒酶活性及细胞凋亡的影响.复旦学报(医学科学版),2001,28(1)：5-8
[62]傅乃武,全兰萍,郭永,等β-榄香烯的抗肿瘤作用和药理学研究.中药1984：9(2)：35-9
[63]秦叔选,钱军,杨爱珍,等.β-榄香烯乳抗肺癌细胞的实验研究.肿瘤防治研究,1996：23(4)：251--5
[64]郝立宏,卢步峰,于丽敏,等.β-榄香烯与阿霉素联合应用对CEM/APM细胞生长的影响大连医科大学学报,2000,22(3)：12
[65]徐学军,周子成,罗元辉,等β-榄香烯诱导人肝癌细胞株SMMC-7721凋亡的研究.第三军医大学学报,1999,21(4)：268-271
[66]马东礼,童善庆.榄香烯对HeLa细胞端粒酶催化亚单位基因表达的作用.中
国癌症杂志2001,11(1)：9-13
[67]Hiyama K, Hiyama E, lshioka S, et al. Telomerase activity in small-cell and non-small-cell lung cancer ·J Natl Cancer Inst.1995,87(12):895-902.
[68]Kerr J FR, Wyllie AH, Currie AR. Apoptosis:a basic biological phenomenon with wide ranging implication in tissue kinetics. Br J Cancer,1972,26:239
[69]Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science,1995,267(5203):1456-1462
[70]Kasagi N, Somyo Y, S hirai H,et al.Al and cancer. J cancer Res.1994:85(9):939-945
[71]Fulvio B,Lisa F,Alfredo F, et a 1. Potentiation of the malignant phenotype of the differentiated ARO thyroid cell line by insertion of the bcl-2 gene. Int J cancer 1999,81:956-962
[72]Green DR. Apoptotic pathways:paper wraps stone blunts scissors. Cell,2000,102:1
[73]G reen DR, Reed Jc. Mitochondrion and apoptosls. Science,1 998,281 (28):1309
[74]Martinous Jc, Desagher S, Antonsson B. Cytochrome C release from mitochondria:all or nothing. Nature cell biology,2000,2:41
[75]Li K, Li Y, Shelton JM, et al. Cytochrome C, deficiency causes embryonic Lethality and attenuates stress-induced apoptosis. Cell,2000,10 1(4):398
[76]Ashkenazi A.Dixit VM. Death receptors:signaling and modulation. Science,1998,281(28):1305
[77]Hussein MR, Haemel AK, Wood GS. Apoptosis and melanoma:molecular mechanisms. Pathol,2003,199(3):275-288
[78]Konno R, Yamakawa H, Utsunomiya H, et al. Expression of suryivin and bcl-2 in the Normal human endometrium. Mol Hum Reprod,2000,6(6):529
[79]Am brosini G,Adida C, Altieri DC. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nat Med,1997, 3(8):917-921.
[80]Altieri DC, Marchisio PC, Marchisio C.Survivin apoptosis:an interloper Between cell death and cell proliferation in cancer. Lab Invest,1999,79 (11):1327-1333.
[81]Tamm I, WangY,Sausville E, et al. IAP-family protein surviving inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. Cancer Res,1998,58(23):5315-5320
[82]Suzuki A, Ito T, Kawano H, et al.Survivin initiates procaspase3/p21 complex formation as a result of interaction with CDK4 to resist Fas-mediated cell death. Oncogene,2000,19 (10):1346
[83]Oconnor DS, Schechner JS, Adida C, et al.Control of apoptosis during angiogenesis by survivin expressi n endothelial cell. Am J Pathol,2000,156 (2):393
[84]Papapetropoulos A, Fulton D, Mubboubi K, et al. Angiopioetin 1 inhibits Endothelial cell.J Biol Chem,2000,275(13):9102
[85]Hirokazu 0, Hitoshi T, Hideyasu 0, et al. Phos-phatidylinositol 3-Kinase/Akt regulates angiotensin 1I-in-duced inhibition of apoptosis in microvascular endothelial cells by governing survivin expression and suppression of caspase-3 activity circ. Res,2004, 94:785
[186]Kishi H, Igawa M, Kikuno N, et al. Expression of the survivin gene in prostate cancer:correlation with clinicopatho-logical characteristics, proliferative activity and apoptosis. J Urol, 2004,171(5):1855
[87]Kren L, Brazdil J, Hermanova M, et al. Prognostic significance of anti-apoptosis proteins surviving and bcl-2 in non-small cell lung carcinomas:a clinicopathologic study of 102 cases. Appl
Immunohistochem Mol Morphol,2004,12 (1):44
[88]Satoh K, Kaneko K, Hirota M, et al. Expression of survivin is correlated with cancer cell apoptosis and is involvedin the development of human pancreatic duct cell tumors. Cancer,2001,92 (2):271-278
[89]Lu CD,Altieri DC, Tanigawa N. Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastriccarcinomas. Cancer Res,1998, 58(9):1808-1812
[90]Adida C, Berrebi D, Peuchmaur M, et al. Anti-apoptosis gene, survivin, and prognoses of neuroblastoma. Lancet,1998, 351(9106):882-883
[91]汪小明,黄循,张选志.膀胱移行细胞癌中凋亡抑制因子survivin的表达及意义.中国现代医学杂志,2004,14(2)：25
[92]Andersen MH, Pedersen L0, Capeller B, et al. Spontaneous cyotoxic Tcell Responses against survivin-derived MHC class I-restricted T-cell epitopes in situ as well as exvivo in cancer patients. Cancer Res,2001,61(16):5964-5968
[93]Altieri DC. Validating survivin as a cancer therapeutic target. Nat Rev Cancer,2003,3(1):46
[94]Marzia P, Mara B, Michelandrea DC. Ribozyme-mediated down-regulation of survivin expression sensitizes human melanoma cells to topotecan in vitro and in vivo. Carcinogenesis,2004,10(5):1093
[95]Enari M. A casepase-activated Dnase that degrades DNA and its inhibitor ICAD during apoptosis. Nature,1998,391:43
[96]Reed JC. Mechanisms of Bcl-2 family protein function and dysfunction in health and disease.Behring Inst Mitt,1996,97:72-100
[97]Jacobson MD. Apoptosis:Bcl-2-related proteins get connected. Curr Biol,1997,7(5):R277-281
[98]Jerry M, Adams, Suzase Cory. Science,1998,281(5381):1322-1326
[99]Thombeny NA, Lazebnik Y. Caspase enemies within. Science,1998, 281(28):1312
[100]MuchmoreS W, Sattler M, Liang H, et al.X-ray and NMR structure of human Bcl-xl, an inhibitor of programmed cell death, Nature,1996,38 1(6580):335-341
[101]Minn AJ, Kettlun CS, Liang H et al. Bcl-xL regulateds apoptosis by heterodimerization-dependent and-independent mechanisms. EMBO J, 1999,18(3):632-643
[102]Shangary S, Johnson DE. Recent a vances in the development.of anticancer agents targeting cell death inhibitors in the Bcl-2. protein family. Leukemia,2003,17(8):1470-1481
[103]Biroccio A, Benassi B, D'Agnanol, et al. c-Myb and Bcl-xoverexpression predicts poor prognosis in colorectal cancer:clinical and experimental findings. AmJ Pathol,2001, 158(4):1289--1299
[104]HattoriT, OokawaN, Fujita R, et al. Heterodimerization of Bcl-2 and Bcl-X(L) With Bax and bad in colorectal cancer. Acta Oncol,2000,39 (4):495-500
[105]Olopade OI, Adeyan ju M0, Safa AR, et al. Overexpression of Bcl-x preotein In primary breast cancer is associated with high tumor grade and nodal metastases. Cancer J Sci Am,1997,3(4):230--237
[106]Zhang C1, Kamarashev J, Qin JZ, et al. Expression of apoptosis regulators in cutaneous T-cell lymphoma (CTCL) cells. J Pathol. 2003,200(2):249-254
[107]Frankel A,R osenK, Filmus J, etal. Induction of anoikis and suppression of human ovarian tumor growth in vivo by down-regulation of Bcl-X. Cancer Res,2001,61(12):4837-4841
[108]Gazzaniga, GradiloneA,S ilvestril,et al. Variable levels of bcl-2, bcl-x and bax mRNA in bladder cancer progression. Oncol Rep,1998,5(4):901-904
[109]Gazzaniga P, G radiloneA,G iuliani L et al. Expression and prognostic Significance of livin, survivin and other apoptosis-related genes in the progression of superficial bladder cancer. Ann Oncol,2003,14(1):85-90
[110]袁静,顾振伦.榄香烯诱导K562细胞凋亡的流式细胞术分析.实用肿瘤杂志,1998,(6)：343-344
[111]范钰,林庚金,钱立平等.榄香烯对胃癌SGC7901细胞bcl-2基因表达及端粒酶活性的影响.上海医学.2001,24(8)：490-492
[112]范钰,林庚金,钱立平等.榄香烯对胃癌SGC-7901细胞C-myc基因表达及端粒酶活性的影响.中国肿瘤临床,2001,28(11)：848-851
[113]刘宇男,.王国良,贾永峰,等.MTT法在榄香烯乳对人膀肌癌T24细胞体外实验中的应用.上海医科大学学报,1997,24(2)：127-130
[114]李传刚,刘用揖,冯秉安,等.0一榄香烯对人BIU-87细胞诱导凋亡的实验研究中国中西医结合外科杂志,1999,5(6)：387-390
[115]李传刚,李墨林,舒晓宏等.0一榄香烯对人膀耽癌BIU-87细胞磷脂代谢转换率及细胞脂膜流动性的影响.中华医学杂志,2004,84(5)：416-417
[116]钱军,秦叔遗,杨爱珍,等榄香烯乳逆转人肺癌细胞的实验研究.肿瘤防治研究,1996：23(5)：29 9-301
[117]吴伟忠,刘康达,汤晓雷,等.p一榄香烯诱导的抗肿瘤免疫保护作用机理初探.中华肿瘤杂志,1999,21(6)：405-408
[118]钱振超,刘金友,赵肃荣,等.获术瘤苗的主动免疫保护效应一羲术抗癌作用原理的探讨.药学学报,1981；16(12)：892-6
[119]金梅,施广霞,朴花,等.榄香烯复合瘤苗主动免疫的抗肿瘤效应.中国肿瘤防治杂志,1999,6(1)：50-51
[120]官成浓,何国章.榄香烯乳配合化疗对进展期胃癌患者免疫功能的影响中国肿瘤临床,2001,28(2)：123-124
[121]陈龙邦,藏静,王靖华.5一榄香烯对荷瘤小鼠免疫功能的影响.肿瘤防治
研究,1998,25(1)：54
[122]张学军,杜权,丁秀萍,等.榄香烯乳对r-DNA转录活性的影响及意义.中国肿瘤临床,1999,26(3)：443-444
[123]郦志军,周君富, 陈周苗,等.榄香烯对肺癌患者血液SOD活性和LPO浓度的影响研究.中国肿瘤临床,1998,25(11)：82 5-853
[124]陈龙邦,藏静,王靖华,等.s一榄香烯对小鼠B16黑色素瘤细胞粘附,运动和间隙连接通讯功能的影响.肿瘤防治研究,1999,26(3)：195-197
[125]颜大海,朱树林,李鑫,等.鸡胚法筛选具有血管生成抑制作用中药.黑龙江医药,1998,11(2)：94
[126]王宝成,郭军,狄剑时,等.榄香烯乳剂与肿瘤多药耐药的基础研究.中国肿瘤临床,1996：23(2)：143--6
[127]Toh Y, Pencil SD, Nicolson GL, A Novel cndidate metastasis associated gene, mtal, differentially expressed in high metastatic mammary adenocarcinom a cell line. J Biological Chemistry,1994;269(37):22958.
[128]Cui Q, Takiguchi S, Matsusue K, e t al.A ssignment of the human metastasis-associated gene 1 (MTA1) to human chromosome band 14q32.3 by fluorescence in situ hybridization. Cytogenet Cell Genet,2001, 93:139-140.
[129]Toh Y,O kiE, Oda S, et al. Overexpression of the mta 1 gene in gastrointestinal carcinomas:correlation with invasion and metastasis. Int J Cancer,1997,74:459-463.
[130]Nicolson GL, NawaA, Toh Y et al.Tumorm etastasis-associated human MTA1 gene and its MTA1 product:role in epithelial cancer cell invasion, proliferation and nuclearre gulation. Clin Exp Metastasis,2003,20 (1):19-24
[131]Toh Y, Kuninaka S, Endo K, et al. Molecular analysis of a candidate metastasis-associated, M TAl:possible inferaction with histone deacetylasel.J Exp Clin Cancer Res,2000;19(1):105
[132]杨磊,丁颜青.肿瘤转移相关基因Mta-1和肿瘤.医学综述2003,9(1)：24-25
[133]唐桥斐,季文越等.转移相关基因表达与喉鳞状细胞癌淋巴结转移的关系.中华耳鼻咽喉科杂志,2003,38(3)：213-216
[134]Matthias D, Rainer K, Sooryanarayana V, etal.The role of metastasis-associated protein 1 in prostate cancer progression. Cancer Research,2004,64:825-829
[135]Mahoney MQ Simpson A, JostM, et al.Metastasis-associatedp rotein(MTA)1 enhances migration, invasion, and anchorage-independent survival of immortalized human eratinocytes. Oncogene,2002,21(14):2161-70
[136]Folkman.J. Role of Angiogenesis in tumor growth and metastasis[J]. Semin Oncol,2002,29:15-18.
[137]Hashizume H, Baluk P, Morkawa S, et al. Openings between defective endothelial cells explain tumor vessel leakiness[J]. Am J Pathol,2000,156(4):1363-1380.
[138]陈文清.莪术油治疗小儿病毒性肺炎疗效观察.江西医学院学报,2004,44(2)：22
[139]王新生,王成芬,王利燕.莪术油葡萄糖注射液治疗病毒性肺炎的疗效观察.中医药研究,2000,16(3)：16,40
[140]徐明,薛业群,葛必胜.莪术油注射液治疗小儿急性支气管炎和肺炎.湖北中医杂志,2004,26(4)：19
[141]叶茂.莪术油葡萄糖注射液治疗婴幼儿间质性肺炎的疗效观察.儿科药学杂志,2004,10(4)：58-59
[142]方淑彩,唐瑜琦.莪术油佐治小儿支原体肺炎的疗效观察.齐齐哈尔医学院学报,2004,25(5)：5 32
[143]仇付丽.莪术油治疗毛细支气管炎122例.中医研究,2004,17(3)：30
[144]戴怡蕃,范联,吴燕玲.莪术油葡萄糖注射液治疗急性上呼吸道感染85例临床观察.广东药学院学报,2001,17(3)：225-227
[145]丛艳华,王双妹,王双红.莪术油治疗婴幼儿肺炎疗效观察.黑龙江医药科学,2001,24(1)：24
[146]王幼萍.莪术油治疗带状疙疹45例.医药导报,2004,23(12)：912-913
[147]焦建萍.莪术油葡萄糖注射液治疗麻疹40例疗效分析山东医药,2001,41(17)：72-73
[148]俞笑林.莪术油治疗婴幼儿病毒性肠炎312例.中国药业,2003,12(3)：68
[149]史玲艾,丁翠,杜静等.莪术油注射液治疗小儿病毒性心肌炎疗效观察.河北中医,2004；26(3)：2 26
[150]李正凡.莪术油葡萄糖注射液治疗小儿流行性腮腺炎42例.湖南中医杂志,2003,19(1)：47
[151]吴建敏.莪术油葡萄糖注射液治疗急性病毒性脑炎疗效观察.海峡药学,2003,15(1)：49-50
[152]袁超英,陈朝俊.莪术油注射液治疗病毒性结膜炎的临床观察.湖北中医杂志,2002,24(11)：34
[153]张辉,罗开国.莪术油滴眼液治疗单纯疙疹性病毒性角膜炎的临床观察.中国医院药学杂志2001,21(8)：489-490
[154]吴玉华,方建华.莪术油治疗病毒性风疹.中国基层医药,2002,9(10)：
[155]张小虎等。莪术油治疗宫颈癌2007,23(12)：912-913
[156]吴万垠,徐凯,刘伟胜等。莪术油微球经肝动脉灌注栓塞治疗原发性肝癌,上海中医药杂志,2004,38(4)：3-6
[157]李智勇,等晓军。莪术油等经植泵治疗姑息性切除术后晚期大肠癌的临床观察.中国中西医结合外科杂志,2002,8(5)：343-344
[158]魏兰福,邹百仓,魏睦新.莪术对实验性功能性消化不良大鼠胃排空的影响[J].南京医科大学学报,2003,23(4)：450-352.
[159]郑方周,李玉升.莪术油治疗小儿科季腹泻临床疗效观察[J].临圻医学专科学校学报,2003,25(3)：397-499
[160]周继红等.莪术油治疗三期褥疮的临床观察。浙江中医药大学学报2008年7月第32卷
[161]李卫彬,陈朝俊.莪术油治疗外感高热症113例临床观察.湖北中医
[J].2003；25(6)：20
[162]宋勉,马利军.清开灵胶囊配合莪术油葡萄糖注射液治疗高热110例[J].光明中医,2001；16(4)：42-43
[163]王培养.莪术油注射液治疗4,JL手足口病疗效观察[J].浙江中西医结合杂志,2003；13(7)：437
[164]沈美珍.莪术油加西瓜霜联合治疗婴幼儿手足口病临床观察[J].宁夏医学杂志。2003；25(2)：108
[165]龚湛潮。白波.莪术油葡萄糖注射液治疗咽结合膜热的疗效观察[J].四川医学,2003；24(8)：840
[166]许刚,李魏等.莪术油治疗皮肤溃疡的临床观察[J].广州中医药大学学报2006,23(5)115-116
[167]李路等.莪术油对皮肤放射损伤的临床观察[J]中国临床杂志.2007：22(3)123-125
[168]陈丽,高骅等。莪术油对甲型肝炎的临床观察[J]中西医结合杂志2008,12(3)113-135
[169]林光勇.莪术油药理作用及临床用药的研究进展[J].广东药学,2002,12(1)：12-14.
[170]李爱群,姚祟舜,许风,等.不同产地莪术挥发油的有效成分f-j].分析测试学报,2002,21(6)：67—69,
[171]Hisashi M. Inhibitory effect and action mechanism of sesquit-erpenes from zedoariae rhizoma on-galactosamine/lipopolysac-charid induced liver injury[J]. Bioorg Med Chem Lett,1998, 8(4):339-341.
[172]Yoshinori S, Tomoko I. Biomimetic transformation of dehydrocur-dione into curcumenol and isocurcumenol and their stereochemis-tries [J]. Tetrahedron Lett,1985,26(7):913-915.
[173]Navarro F, Souza MM. Phytochemical analysis and analgesicproperties of Curcuma zedoaria grown in Brazil [J]. Phytomedi-cine,2002,9(5): 427-428.