亚硒酸钠联合阿霉素前体药通过调控活性氧水平及线粒体功能促进胃癌细胞SGC-7901凋亡  

Sodium selenite combined with adriamycin precursor drug promoted the apoptosis of gastric cancer cells SGC-7901 by regulating reactive oxygen species level and mitochondrial function

作　　者：谭子富 张碧涛 杨小琴 陈元杏 李家权 张娟 孙建华 Tan Zifu;Zhang Bitao;Yang Xiaoqin;Chen Yuanxing;Li Jiaquan;Zhang Juan;Sun Jianhua(Hubei Selenium and Human Health Institute,the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture,Enshi 445000,Chin;Department of Gastrointestinal Surgery,the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture,Enshi 445000,Chin;Medical School of Hubei University for Nationalities,Enshi 445000,China)

机构地区：[1]恩施州中心医院湖北硒与人体健康研究所,445000 [2]恩施州中心医院湖胃肠外科,445000 [3]湖北民族学院医学院,恩施445000

出　　处：《中华实验外科杂志》2018年第11期2075-2078,共4页Chinese Journal of Experimental Surgery

基　　金：湖北省自然科学基金（2016CFB668）;恩施州中心医院“硒与人体健康”科研项目;国家自然科学基金（81770283）;武汉市腹膜癌临床医学研究中心资助项目（2015060911020462）

摘　　要：目的探讨亚硒酸钠（Na2SeO3）联合阿霉素前体药（PADM）对胃癌细胞SGC-7901活性氧水平、线粒体功能的影响及其促凋亡机制。方法取对数生长期SGC-7901细胞，分为对照组、2．93μg／ml Na2SeO3处理组、2μg／ml PADM处理组及Na2SeO3＋PADM联合处理组。48h后，检测各组细胞的活性氧（ROS）水平、凋亡状况、细胞内线粒体膜电位变化、线粒体膜通透性以及凋亡相关蛋白的表达。结果与对照组细胞ROS水平比较，Na2SeO3、PADM组以及联合处理组显著升高（均P=0．000）；与对照组细胞凋亡率比较，Na2SeO3、PADM组以及联合处理组显著增加（均P=0．000）；与对照组细胞线粒体膜电位去极化水平比较，Na2SeO3、PADM组以及联合处理组显著升高（均P=0．000）；与对照组细胞线粒体通透性转换孔（mPTP）活性水平比较，Na2SeO3、PADM组以及联合处理组显著升高（均P=0．000）。此外，与对照组比较，各药物处理组Cyt C、p53、B细胞淋巴瘤／白血病-2相关X蛋白（bax）、裂解的半胱氨酰天冬氨酸特异性蛋白酶9（Cleaved-Caspase）-9和Cleaved-Caspase-3蛋白表达水平明显升高，而B细胞淋巴瘤／白血病-2（bcl-2）蛋白水平明显降低。结论亚硒酸钠联合阿霉素前体药PADM能显著促进胃癌细胞SGC-7901凋亡，其机制可能与提升细胞ROS水平、增高细胞线粒体膜电位去极化水平以及线粒体膜通透性进而激活线粒体凋亡信号通路密切相关。Objective To investigate the effect of sodium selenite combined with prodrug of adriamyein （PADM） on reactive oxygen species （ROS） level and mitochondrial function of gastric cancer cells SGC-7901 and the apoptotic mechanism. Methods SGC-7901 cells in logarithmic growth stage were taken and divided into the control group, 2.93 μg/ml sodium selenite （Na2SeO3） treatment group, 2 μg/ml PADM treatment group and Na2SeO3 ＋ PADM combined treatment group. After 48 h, ROS and apoptosis levels, the changes of mitochondrial membrane potential in cells, the permeability of mitochondrial membrane and the expression of apoptosis-related proteins were detected. Results As compared with control group, Na2SeO3 group, the ROS levels in PADM group and combined treatment group were significantly increased （all P=0. 000）. As compared with the control group, the apoptosis rate in Na2SeO3 group, PADM group, and combined treatment group increased significantly （ all P=0.000）. As compared with the control group, the level of mitochondrial membrane potential depolarization in Na2SeO3 group, PADM group and combined treatment group increased significantly （ all P=0. 000）. As compared with the control group, the mitochondrial permeability transition pore （mPTP） activity level in Na2SeO3 group, PADM group and combined treatment group increased significantly （ all P=0.000）. In addition, as compared with the control group, the expression levels of cytochrome C （Cyt C）, p53, B cell lymphoma/leu-kemia-2 associated X protein （ bax）, Cleaved - cysteinyl aspartate-specific protease （Caspase）-9 and Cleaved-Caspase-3 in each drug treatment group were significantly increased, and those of B cell lymphoma/leukemia-2 （bcl-2） protein was significantly decreased. Conclusion Sodium selenite in combination with adriamycin precursor drug PADM can significantly promote the gastric cancer SGC-7901 cells apoptosis, which may be closely related to the enhancement of cell ROS level, the increase of cell mito-chon

关 键 词：胃癌 亚硒酸钠 阿霉素前体药 活性氧 线粒体 凋亡 

分 类 号：R96[医药卫生—药理学]