MS-275通过上调ROS释放选择性杀伤胃癌细胞  

MS-275 selectively killing gastric cancer cells by up regulating ROS release

作　　者：黄辞[1] 吴智群[1] 宫卫东[1] 何志[2] 

机构地区：[1]第四军医大学唐都医院介入科,陕西西安710038 [2]第四军医大学唐都医院整形科,陕西西安710038

出　　处：《现代肿瘤医学》2014年第9期2001-2006,共6页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(No:30973464)

摘　　要：目的:研究组蛋白去乙酰化酶抑制剂MS-275通过线粒体凋亡途径,选择性杀伤胃癌细胞的具体作用机制。方法:MS-275分别处理GES-1、MKN-45细胞,通过WST-1法检测细胞存活率,分析MS-275细胞毒性及选择性杀伤作用;通过流式细胞术检测线粒体膜电位变化,及ROS抑制剂对MS-275凋亡诱导作用的影响;Western blot、PCR分别检测处理后胃癌细胞中p21、p57、cyclin D1、cyclin E1、和TBP-2的mRNA及蛋白水平表达情况。结果:MS-275对正常胃黏膜上皮细胞GES-1存活率无显著性影响,但对胃癌细胞MKN-45影响显著(P<0.05)。MS-275对胃癌细胞MKN-45线粒体膜电位影响不显著,但能够诱导ROS显著升高,ROS抑制剂显著降低由MS-275诱导的ROS释放。MS-275显著激活肿瘤抑制基因p21、p57、TBP-2以及细胞周期蛋白相关基因cyclin D1、cyclin E1的表达。结论:MS-275通过促进细胞周期阻滞因子、凋亡诱导基因、肿瘤抑制基因的表达,诱导ROS生成,选择性杀伤胃癌细胞。Objective:To study the specific mechanism in which the histone deacetylase inhibitor MS-275 selectively killed gastric cancer cells through the mitochondrial apoptosis pathway. Methods:GES- 1,MKN- 45 cells were treated by MS- 275. By using viability assay WST- 1 to analyze the cell cytotoxicity and the selectively killing effect of MS- 275. Detect the changes of the mitochondrial membrane potential,and the effects on ROS inhibitor to the apoptosis induced of MS- 275 by flow cytometry. Detect the mRNAs expression and protein levels of p21,p57,cyclin D1,cyclin E1,TBP- 2 after treatment by Western blot and PCR methods. Results:There was no significant effect of MS- 275 to normal gastric mucosa epithelial cells GES- 1 on survival,but the impact on gastric cancer cell MKN- 45 was significantly(P < 0. 05). The impact on MS- 275 to the mitochondrial membrane of gastric cancer cell MKN- 45 was not significant,but which could induce a significant increase in ROS,and ROS inhibitors could significantly reduced the MS- 275- induced ROS release. MS- 275 significantly activated oncogene p21,p57,TBP- 2,cyclin- related genes cyclin D1 and cyclin E1 expression. Conclusion:MS- 275 can selectively kill gastric cancer cells by inducing ROS generation through promoting the expression of cell cycle arrest factors,apoptosis induced genes and tumor suppressor genes.

关 键 词：MS-275 胃癌 胃癌细胞系 GES-1 MKN-45 ROS 

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