二甲双胍逆转卵巢癌细胞对紫杉醇耐药性的研究  

A Research into the Reversal Effect of Metformin on Drug Resistance of Paclitaxel in Human Ovarian Carcinoma Cells

作　　者：霍静[1] 黄燕[2] 宋少娟[1] 刘丰其 宋丽华[4] 

机构地区：[1]长治医学院基础医学部生物学教研室,046000 [2]长治医学院基础医学部生化教研室 [3]长治医学院基础医学部 [4]长治医学院药学系药理教研室

出　　处：《长治医学院学报》2017年第3期161-165,共5页Journal of Changzhi Medical College

基　　金：长治医学院科技创新团队(CX201413);长治医学院科技启动基金项目(QDZ201501)

摘　　要：目的:探讨二甲双胍对卵巢癌耐药细胞A2780/Taxol紫杉醇耐药性的逆转作用及可能的机制。方法:实验分为对照组和二甲双胍作用组(10mM、20mM、30mM)。药物作用48h后,使用CCK-8法检测细胞A2780/Taxol的增殖;Hoechst 33258染色检测细胞凋亡;划痕实验检测细胞的迁移能力;流式细胞术检测细胞内Rh123的积累;蛋白免疫印迹检测凋亡相关蛋白cleaved Caspase-3及Bcl-2蛋白的表达。结果:二甲双胍抑制细胞A2780/Taxol的增殖,实验组与对照组相比差异有统计学意义(P<0.05);实验组细胞染色质凝集,细胞凋亡率增高(P<0.05);细胞的迁移能力下降,实验组与对照组差异明显(P<0.05);10mM、20mM组细胞内Rh123累积量增加,与对照组差异明显(P<0.05);凋亡相关蛋白cleaved Caspase-3表达上调,Bcl-2蛋白表达下降。结论:二甲双胍可能通过上调cleaved Caspase-3表达、下调Bcl-2蛋白表达,启动线粒体内源性凋亡途径来逆转卵巢癌细胞A2780/Taxol对紫杉醇的耐药性。ObjectiveTo investigate whether metformin can reverse drug-resistance of ovarian cancer cell A2780/Taxol to Taxol ？ and explore its possible mechanisra Methods：The experiment was divided into control group and metformin group（10 mM20 mM%30 mM）. Taxol-resistance cell A2780/Taxol was used in this study. After 48 hours of drug effects？the inliibition of proliferation of A2780/Taxol cells was detected by cell count kit-8 （CX3K-8） assay after treatment with metformia Hoechst 33258 was used to detect apoptosis. Cell scratch assay was used to detect the changes of the cell migratioa ＂I＇he accumulation of Rhl23 in the cells was tested by flow cytometry. The expression of Caspase-3 and Bel-2 were tested by Western blotting. Results：Metformin inliibited the proliferation of A2780/Taxol cells. The difference was statistically significant between the cxrimental group and the control group（P〈0. 05）. The afX）ptosis rate of the cell was increased by metformia The migration ability and the drug efflux of the cells decreased,and the concentration groups of lOmM and 20 mM were significantly different from the control group （P〈0 . 01）. Metformin could reduce the expression of cleaved Caspase-3 and decrease the expression of Bel-2. Conclusion： Metformin can reverse the paclitaxel-resistance in human ovarian cancer cell line A2780/Taxol by up- rulating cleaved Caspas eression ,dowivregulating -2 protein expression and initiating mitochondrial

关 键 词：卵巢癌 耐药性 二甲双胍 细胞凋亡 

分 类 号：R737[医药卫生—肿瘤]