表柔比星诱导的保护性自噬抑制了胃癌MGC803细胞的凋亡  

Protective autophagy inhibits epirubicin-induced apoptosis in gastric cancer MGC803 cells

作　　者：徐玲[1] 张晔[1] 刘云鹏[1] 曲秀娟[1] 朱轶轲[1] 刘静[1] 侯科佐[1] 

机构地区：[1]中国医科大学附属第一医院肿瘤内科,辽宁沈阳110001

出　　处：《现代肿瘤医学》2011年第5期829-832,共4页Journal of Modern Oncology

基　　金：国家自然科学基金项目(No.30770993);2008年辽宁省高等学校优秀人才支持计划项目(No.2008RC55);中国医科大学附属第一医院科学研究基金项目(No.fsfh1003)

摘　　要：目的:明确表柔比星作用胃癌MGC803细胞后自噬的存在,探讨自噬在表柔比星诱导胃癌细胞凋亡中的作用。方法:表柔比星处理胃癌MGC803细胞,MTT检测细胞增殖能力,流式细胞术检测细胞凋亡,Western blot检测蛋白表达。结果:1.2μg/ml的表柔比星作用MGC803细胞24h,细胞凋亡率为(23.56±3.49)%,并且多聚ADP-核糖聚合酶(PARP)蛋白发生了裂解。与此同时,1.2μg/ml的表柔比星导致了微管相关蛋白轻链3-Ⅱ(LC3-Ⅱ)蛋白的提高和细胞自噬体的增多。提示表柔比星同时诱导了凋亡和自噬的发生。与单药表柔比星相比,自噬抑制剂氯喹联合表柔比星明显提高了细胞增殖抑制率[(71.79±4.34)%vs(47.70±3.67%),P<0.05]。而且,氯喹联合表柔比星诱导了更明显的MGC803细胞凋亡[(43.98±4.67)%vs(25.09±3.29%),P<0.05]。结论:表柔比星诱导的保护性自噬抑制了胃癌MGC803细胞的凋亡。自噬抑制剂联合表柔比星为胃癌提供了新的治疗策略。Objective：To identify the presence of epirubicin-induced autophagy in MGC803 gastric cancer cells,and to reveal the effect of autophagy on epirubicin-induced apoptosis.Methods： MGC803 gastric cancer cells were cultured and treated with epirubicin.Cell proliferation was measured using MTT assay.Cell apoptosis was determined by flow cytometry.The expression of proteins was detected by Western blot.Results： Treated with 1.2μg/ml epirubicin for 24 h,the rate of cell apoptosis was（23.56±3.49）%,and poly ADP-ribose polymerase（PARP） protein was clearaged.At the same time,treated with 1.2μg/ml epirubicin leaded to the increase of microtubule-associated protein light chain 3-Ⅱ（LC3-Ⅱ） protein and the cellular autophagosome.This indicated that epirubicin induced both apoptosis and autophagy.Compared to epirubicin alone,the combination of autophagy inhibitor chlorochine and epirubicin significantly enhanced the inhibition rate of cell proliferation [（71.79±4.34）% vs（47.70±3.67）%,P〈0.05].Moreover,chlorochine with epirubicin induced more obvious apoptosis in MGC803 cells [（43.98±4.67）% vs（25.09±3.29）%,P〈0.05].Conclusion： Epirubicin-induced protective autophagy prevented cell apoptosis in MGC803 gastric cancer cells.The combination of autophagy inhibitor and epirubicin provided a new therapeutic strategy for gastric cancer.

关 键 词：自噬 凋亡 表柔比星 胃癌 

分 类 号：R73-361[医药卫生—肿瘤] R735.2[医药卫生—临床医学]