MLN4924诱导胃癌细胞MGC-803发生线粒体自噬及细胞凋亡的初步研究  

A preliminary study of mitophagy and apoptosis induced by MLN4924 in MGC-803 cells

作　　者：邱志兵 邱冬妮 丁伟群 QIU Zhibing;QIU Dongni;DING Weiqun(Department of Digestive Diseases,Huashan Hospital Affiliated to Fudan University,Shanghai 200040,China)

机构地区：[1]复旦大学附属华山医院消化科,200040

出　　处：《国际消化病杂志》2020年第6期390-395,共6页International Journal of Digestive Diseases

基　　金：上海市卫生和计划生育委员会(2016Y0153);科技部重大专项(2018ZX10302206-005-007)。

摘　　要：目的研究MLN4924是否可以诱导胃癌细胞发生线粒体自噬及细胞凋亡。方法采用MTT法检测MLN4924对胃癌细胞MGC-803增殖的影响。采用流式细胞术检测MLN4924诱导MGC-803发生细胞凋亡的情况。采用定量聚合酶链反应(qPCR)及蛋白免疫印迹法(Western Blot)检测线粒体自噬相关通路的重要基因的转录及蛋白表达情况。构建自噬LC3B双标慢病毒稳转MGC-803细胞系,观察线粒体自噬的产生。结果MLN4924可显著抑制胃癌细胞MGC-803的增殖,并呈明显的剂量效应关系。MLN4924处理24 h后,可诱导MGC-803细胞发生凋亡,并且线粒体自噬相关通路的关键基因LC3B、p62及PINK1的mRNA和蛋白水平也明显升高。用MLN4924处理LC3B双标慢病毒稳转细胞模型后,可发现线粒体自噬现象。结论MLN4924可诱导MGC-803细胞发生线粒体自噬及细胞凋亡。Objective This paper intends to study whether MLN4924 can induce mitochondrial autophagy and apoptosis in gastric cancer cells.Methods The MTT assay was used to detect the effect of MLN4924 on the proliferation of gastric cancer cell MGC-803.Flow cytometry was used to detect the apoptosis of MGC-803 induced by MLN4924.Quantitative polymerase chain reaction(qPCR)and western blot were used to detect the transcription and protein expression of important genes in mitochondrial autophagy-related pathways.The LC3B-stubRFP-sensGFP stable transfected MGC-803 cell line was constructed to observe the production of mitochondrial autophagy.Results MLN4924 could significantly inhibit the proliferation of gastric cancer cell MGC-803,and shows an obvious dose-effect relationship.After 24 hours of treatment with MLN4924,MGC-803 cells can be induced to undergo apoptosis,and the transcription and protein levels of key genes LC3B,p62,and PINK1 in mitochondrial autophagy-related pathways are also increased significantly.After processing the LC3B-stubRFP-sensGFP stable transfected MGC-803 cell line using MLN4924,mitochondrial autophagy could be found.Conclusion MLN4924 can induce mitochondrial autophagy and apoptosis in MGC-803 cells.

关 键 词：MLN4924 胃癌 细胞凋亡 线粒体自噬 

分 类 号：R73[医药卫生—肿瘤]