参芪抑瘤方联合顺铂对MFC荷瘤小鼠瘤组织 XIAP、PTEN表达的影响
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摘要
目的:研究参芪抑瘤方联合顺铂对MFC荷瘤小鼠瘤组织连锁凋亡抑制蛋(XIAP)及磷酸酶和张力蛋白同源缺失性基因(PTEN)表达的影响。方法:建立MFC荷瘤小鼠模型进行体内抗肿瘤试验,将50只荷瘤小鼠随机分为模型组、顺铂组、参芪抑瘤方低剂量组(中药低组)、参芪抑瘤方高剂量组(中药高组)、参芪抑瘤方低剂量联合顺铂组(联合低组)、参芪抑瘤方高剂量联合顺铂组(联合高组),连续灌胃给药15 d,观察肿瘤生长情况以及小鼠一般情况,15 d后处死小鼠,剥取瘤组织称重,计算抑瘤率;实时荧光定量PCR技术(qRT-PCR)和免疫组织化学技术(IHC)分别检测肿瘤组织中XIAP、PTEN mRNA和蛋白的表达情况。结果:不同剂量组抑瘤率依次为顺铂组55.25%,参芪抑瘤方低、高剂量组分别为27.7%和30.58%,芪抑瘤方低、高剂参量联合顺铂组分别为66.3%和67.78%。联合用药组优于单纯用药组,差异具有统计学意义(P<0.01)。与模型组相比,顺铂组、中药组、联合组中XIAP mRNA及蛋白的表达均降低,PTEN mRNA及蛋白的表达升高,差异有统计学意义(P<0.01)。与顺铂组、中药低组和中药高组相比,联合低组和联合高组中XIAP mRNA及蛋白的表达均降低,PTEN mRNA及蛋白的表达升高,差异有统计学意义(P<0.01)。结论:参芪抑瘤方具有一定的抗MFC胃癌移植瘤作用,并与顺铂联用具有减毒增效作用。其作用可能是通过下调瘤组织中XIAP的表达,上调PTEN的表达有关。
Objective:To study the effect of Shenqi Anti Tumor Recipe combined with cisplatin on the expression of apoptosis inhibiting egg(XIAP) and phosphatase and homology deleted gene(PTEN) in tumor tissues of MFC tumor-bearing mice.Methods:MFC tumor-bearing mice model was established to carry out anti tumor test in vivo,50 tumor-bearing mice were randomly divided into model group(M),cis-diamin-odichlor platinum group(DDP),low dosage of Chinese medicine group(TCML),high dosage of Chinese medicine group(TCMH),low dosage of combination group(TCML+DDP),high dosage of combination group(TCMH+DDP),with 8 animals in each group.Another 8 healthy mice were regarded as normal control group(N).Continuous intragastric administration lasted for 15 days.The tumor growth and the general condition of the mice were observed and the mice were killed 15 days later.The tumor tissue was weighed and the tumor inhibition rate was calculated.Real time fluorescence quantitative PCR(qRT-PCR) and immunohistochemistry(IHC) were used to detect the expressions of XIAP,PTEN mRNA and protein in tumor tissues.Results:The tumor inhibition rate in DDP different dosage groups was 55.25%,while the Chinese medicine group′s inhibiting rate were 27.7% and 30.58% respectively.At the same time,the inhibiting rates of combination group were 66.3% and 67.78% respectively.TCML+DDP group was better than single groups and the difference was statistically significant(P<0.01).Compared with the M group,the expressions of XIAP mRNA and protein in DDP group,Chinese medicine group and combined group decreased and the expressions of PTEN mRNA and protein increased.The difference was statistically significant(P<0.01).Compared with DDP group,TCML and TCMH group′s expressions of XIAP mRNA and protein decreased and the expression of PTEN mRNA and protein increased.The difference was statistically significant(P<0.01).Conclusion:Shenqi Anti Tumon Recipe has a certain effect of anti-MFC gastric cancer transplanting,and combined with cis-diamin-odichlor platinum it has a synergistic effect.Its role may be down regulating the expression of XIAP in tumor tissue and up regulating PTEN expression.
Objective:To study the effect of Shenqi Anti Tumor Recipe combined with cisplatin on the expression of apoptosis inhibiting egg(XIAP) and phosphatase and homology deleted gene(PTEN) in tumor tissues of MFC tumor-bearing mice.Methods:MFC tumor-bearing mice model was established to carry out anti tumor test in vivo,50 tumor-bearing mice were randomly divided into model group(M),cis-diamin-odichlor platinum group(DDP),low dosage of Chinese medicine group(TCML),high dosage of Chinese medicine group(TCMH),low dosage of combination group(TCML+DDP),high dosage of combination group(TCMH+DDP),with 8 animals in each group.Another 8 healthy mice were regarded as normal control group(N).Continuous intragastric administration lasted for 15 days.The tumor growth and the general condition of the mice were observed and the mice were killed 15 days later.The tumor tissue was weighed and the tumor inhibition rate was calculated.Real time fluorescence quantitative PCR(qRT-PCR) and immunohistochemistry(IHC) were used to detect the expressions of XIAP,PTEN mRNA and protein in tumor tissues.Results:The tumor inhibition rate in DDP different dosage groups was 55.25%,while the Chinese medicine group′s inhibiting rate were 27.7% and 30.58% respectively.At the same time,the inhibiting rates of combination group were 66.3% and 67.78% respectively.TCML+DDP group was better than single groups and the difference was statistically significant(P<0.01).Compared with the M group,the expressions of XIAP mRNA and protein in DDP group,Chinese medicine group and combined group decreased and the expressions of PTEN mRNA and protein increased.The difference was statistically significant(P<0.01).Compared with DDP group,TCML and TCMH group′s expressions of XIAP mRNA and protein decreased and the expression of PTEN mRNA and protein increased.The difference was statistically significant(P<0.01).Conclusion:Shenqi Anti Tumon Recipe has a certain effect of anti-MFC gastric cancer transplanting,and combined with cis-diamin-odichlor platinum it has a synergistic effect.Its role may be down regulating the expression of XIAP in tumor tissue and up regulating PTEN expression.
引文
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[12] QU Y,XIA P,ZHANG S,et al. Silencing XIAP suppresses osteosarcoma cell growth,and enhances the sensitivity of osteosarcoma cells to doxorubicin and cisplatin[J]. Oncology Reports,2015,33(3):1177-1184.
[13] KUNZE D,KAI K,ERDMANN K,et al. Simultaneous siRNA-mediated knockdown of antiapoptotic BCL2,Bcl-x L,XIAP and survivin in bladder cancer cells[J]. Int J Oncol,2012,41(4):1271-1277.
[14] JIANG C,TANT,Yi X P,et al. Lentivirus-mediated shRNA targeting XIAP and survivin inhibit SW1990 pancreatic cancer cell proliferation in vitro and in vivo[J]. Molecular Medicine Reports,2011,4(4):667-674.
[15]郭长青,邵经浩,卢瑞利,等.胃癌组织中Beclin 1和PTEN蛋白的表达[J].郑州大学学报医学版,2010,45(3):463-466.
[16]刘敏丽,张生军,成延萍,等. PTEN蛋白在胃癌中的表达及预后[J].山西医科大学学报,2010,41(6):504-506.
[17] HENG Wu,VIKAS Goel,FRANK G,et al. PTEN signaling pathways in melanoma[J]. Oncogene,2003,22(20):3113-3122.
[2] YU H,WANG Y,GE X,et al.Depression and survival in Chinese patients with gastric cancer:a prospective study[J].Asian Pacific Journal of Cancer Prevention Apjcp,2012,13(1):391.
[3] 袁媛.胃癌病因及早诊早治[M].北京:科学出版社,2013.
[4] QUIROS R M,DESAI D C.Multidisciplinary approach for the treatment of gastric cancer[J].Minerva Gastroenterologica E Dietologica,2011,57(1):53-68.
[5] 冯颖,吴成亚,李杰.中医药治疗胃癌的优势及可能机制研究进展[J].辽宁中医志,2017,44(1):200-203.
[6]李红亮,吴红彦,李海龙,等.参芪抑瘤方抑制胃癌细胞MKN-45增殖和侵袭转移作用机制[J].中国实验方剂学杂志,2016,22(22):129-133.
[7]马春林,吴红彦,李海龙,等.参芪抑瘤方药物血清对胃癌MGC-803细胞增殖的影响[J].中国中医药信息杂志,2017,24(3):53-56.
[8]陈奇.中药药效研究思路与方法[M].北京:人民卫生出版社,2005:1001.
[9]徐淑云.药理实验方法学[M].北京:人民卫生出版社,2005:1762.
[10]金惠铭,王建枝.病理生理学[M].北京:人民卫生出版社,2008:110-116.
[11] KIM D W,SEO S W,CHO S K,et al. Targeting of cell survival genes using small interfering RNAs(siRNAs)enhances radiosensitivity of Grade II chondrosarcoma cells[J]. Journal of Orthopaedic Research,2007,25(6):820-828.
[12] QU Y,XIA P,ZHANG S,et al. Silencing XIAP suppresses osteosarcoma cell growth,and enhances the sensitivity of osteosarcoma cells to doxorubicin and cisplatin[J]. Oncology Reports,2015,33(3):1177-1184.
[13] KUNZE D,KAI K,ERDMANN K,et al. Simultaneous siRNA-mediated knockdown of antiapoptotic BCL2,Bcl-x L,XIAP and survivin in bladder cancer cells[J]. Int J Oncol,2012,41(4):1271-1277.
[14] JIANG C,TANT,Yi X P,et al. Lentivirus-mediated shRNA targeting XIAP and survivin inhibit SW1990 pancreatic cancer cell proliferation in vitro and in vivo[J]. Molecular Medicine Reports,2011,4(4):667-674.
[15]郭长青,邵经浩,卢瑞利,等.胃癌组织中Beclin 1和PTEN蛋白的表达[J].郑州大学学报医学版,2010,45(3):463-466.
[16]刘敏丽,张生军,成延萍,等. PTEN蛋白在胃癌中的表达及预后[J].山西医科大学学报,2010,41(6):504-506.
[17] HENG Wu,VIKAS Goel,FRANK G,et al. PTEN signaling pathways in melanoma[J]. Oncogene,2003,22(20):3113-3122.
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