保护性自噬对5-FU诱导的胃癌细胞凋亡的抑制作用  

Protective autophagy inhibits 5-FU-induced apoptosis in human gastric cancer cell line MGC803

作　　者：徐玲[1] 曲秀娟[1] 刘云鹏[1] 刘静[1] 丁小娣[1] 侯科佐[1] 张晔[1] 

机构地区：[1]中国医科大学附属第一医院肿瘤内科,辽宁省沈阳市110001

出　　处：《世界华人消化杂志》2011年第8期777-781,共5页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.30770993;中国医科大学附属第一医院科学研究基金资助项目;Nofsfh1003;辽宁省高等学校优秀人才支持计划基金资助项目;No2008RC55;辽宁省高等学校重点实验室基金资助项目;No.2008S246~~

摘　　要：目的:明确5-FU处理胃癌MGC803细胞后自噬的存在,并探讨自噬在5-FU诱导凋亡中的作用.方法:5-FU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.荧光显微镜观察自噬的发生.结果:0.1-1000mg/L的5-FU作用MGC803细胞48h,抑制细胞增殖50%的药物浓度(IC50)为2.07mg/L±1.14mg/L.2mg/L和5mg/L的5-FU作用细胞48h,细胞凋亡率分别为22.46%±3.21%和32.27%±4.52%.同时,5-FU诱导细胞自噬的发生,观察到LC3的点状聚集和LC3-II蛋白的提高.并且,5-FU抑制了PI3K/Akt/mTOR通路的活性.用氯喹抑制自噬明显提高了5-FU诱导的细胞凋亡(P<0.05).结论:5-FU诱导保护性自噬并阻止了胃癌MGC803细胞的凋亡.5-FU和自噬抑制剂的联合应用可能是很有希望的胃癌治疗策略.AIM： To investigate whether 5 uorouracil （5-FU） induces autophagy in human gastric cancer cell line MGC803 and to identify the role of autophagy in 5-FU-induced cell apoptosis.METHODS： After cultured MGC803 cells were treated with 5-FU,cell proliferation was measured using MTT assay;cell apoptosis was de-termined by ow cytometry;protein expression was detected by Western blot;and autophagy was observed by uorescent microscopy.RESULTS： The concentration of 5-FU inducing a 50% inhibition of cell proliferation （IC50） was 2.07 mg/L ± 1.14 mg/L in MGC803 cells.After treatment with 2 and 5 mg/L 5-FU for 48 h,the rates of cell apoptosis were 22.46% ± 3.21% and 32.27% ± 4.52%,respectively.Autophagy,characterized by an increase in the number of punctate LC3 dots and the level of LC3-II protein,was observed in cells treated with 5-FU.The activity of the PI3K/Akt/mTOR pathway was inhibited by 5-FU treatment.Inhibition of autophagy with chlorochine signif icantly enhanced 5-FU-induced apoptosis （P 0.05）.CONCLUSION： 5-FU-induced protective autophagy prevents MGC803 cells from apoptosis.Combination therapy with 5-FU and autophagy inhibitors may be a promising therapeutic strategy for gastric cancer.

关 键 词：自噬 5-氟尿嘧啶 胃癌 凋亡 

分 类 号：R735.2[医药卫生—肿瘤]