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Molecular mechanism for metformin to enhance pro-apoptotic effect of sorafenib in HepG2 cells

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Author:: No author available

Journal Title:: World Chinese Journal of Digestology

Issue:: 14

DOI:: 10.11569/wcjd.v28.i14.581

Key Word:: 二甲双胍;索拉菲尼;HepG2细胞;分子机制

Abstract：背景延长进展期肝癌生存时间是目前临床上一大难点.索拉菲尼(Sorfenib,Sot)是目前唯一用于治疗进展期肝癌的靶向药物,但其耐药成为一个问题.本研究拟通过实验研究二甲双胍(Metformin,Met)增强Sor的疗效,为进展期肝癌的治疗提供参考.目的探讨Met增强Sor诱导人肝癌HepG2细胞凋亡及潜在分子机制.方法 MTT法检测Met、Sor二者联合对人肝癌HepG2细胞的增殖抑制作用,流式细胞仪测定各组的凋亡率;Western blot检测各组表达Caspase-3、Bax、AMPK、P53及mTORCl水平.结果 MTT结果显示Met和Sor联合对HepG2细胞的增殖抑制作用强于单药组、对照组、Met组、Sor组、联合用药组的细胞相对活力分别为100％、79.96％±4.41％、85.33％±1.00％、68.60％±4.02％,差别有统计学意义(P＜0.05);流式细胞分析结果显示Met和Sor联合对HepG2细胞的凋亡诱导作用强于单药组、对照组、Met组、Sor组、联合用药组的凋亡率分别为4.47％±1.93％、13.73％±1.18％、9.50％±0.20％、29.03％±0.35％,差别有统计学意义(P＜0.05);Western blot显示,与对照组及单药组相比,联合用药组Caspase-3、Bax、AMPK、P53的表达增加,而mTORCl的表达减少.结论 Met可增强Sor诱导人肝癌HepG2细胞凋亡.

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