联合自噬抑制剂增加PI3K/mTOR抑制剂NVP-BEZ235诱导的结肠癌细胞凋亡  

Inhibition of autophagy enhances dual PI3K/mTOR inhibitor NVP-BEZ235 induced apoptosis of human colon adenocarcinoma cell lines

作　　者：斯庆图娜拉[1] 

机构地区：[1]鄂尔多斯市中心医院,内蒙古鄂尔多斯017000

出　　处：《中国实验诊断学》2015年第10期1632-1635,共4页Chinese Journal of Laboratory Diagnosis

摘　　要：目的探讨自噬对I3K/mTOR抑制剂NVP-BEZ235诱导的人结肠腺癌DLD1细胞凋亡的影响。方法PI3K/mTOR抑制剂NVP-BEZ235和(或)自噬抑制剂3-MA处理人结肠腺癌DLD1细胞,MTT法检测细胞生存率,流式细胞术检测细胞凋亡率的变化,Western Blot检测凋亡相关蛋白的表达。结果不同浓度的NVP-BEZ235作用于人结肠腺癌DLD1细胞24h后,MTT及流式细胞术结果显示,明显地抑制了细胞增殖,并增加了细胞凋亡率,同时观测到凋亡相关蛋白Caspase-3表达升高;采用3-MA特异性抑制自噬活性后,明显地增加了NVP-BEZ235诱导的细胞凋亡率;同时,检测到凋亡相关蛋白Caspase-3的表达上调。结论自噬在NVP-BEZ235诱导的人结肠腺癌DLD1细胞凋亡的过程中起保护作用,3-MA抑制自噬后,促进了NVP-BEZ235诱导人结肠腺癌DLD1细胞凋亡,联合应用PI3K/mTOR抑制剂NVP-BEZ235和自噬抑制剂3-MA有望成为人结肠癌的新治疗策略。Objective To investigate effects of inhibition of autophagy on NVP-BEZ235-induced apoptosis in human colon adenocarcinoma cell line DLD1.Methods After the DLD1 cells were treated with NVP-BEZ235and/or 3-MA,cell viability was detected by an MTT assay.The rate of cell apoptosis was detected using flow cytometry.The expression of apoptosis-related protein were detected by Western blot.Results The cells were treated with varied concentration of NVP-BEZ235 for 24h.According to the results of MTT and flow cytometry,the rate of cell proliferation decreased,and the rate of cell apoptosis increased in the dose of NVP-BEZ235.Meanwhile,the expression of apoptosis-related protein,cleaved caspase 3,was increased.However,after autophagy was inhibited by 3-MA,the rate of cell viability was obviously decreased.Meanwhlie,we detected that inhibition of autophagy enhanced the rate of NVP-BEZ235-induced apoptosis and the expression of apoptosis-related protein were obviously increased.Conclusion Autophagy protected human colon adenocarcinoma cell line DLD1 from NVP-BEZ235-induced apoptosis.In addition,the blockage of autophagy could enhance NVP-BEZ235-induced apoptosis.The combined therapy of NVP-BEZ235 and 3-MA may be a promising therapeutic strategy for human colon adenocarcinoma cell line DLD1.

关 键 词：自噬 PI3K/mTOR抑制剂NVP-BEZ235 3-MA 凋亡 人结肠癌 

分 类 号：R735.35[医药卫生—肿瘤]