MS-275对胃腺癌细胞抑制作用及其机制研究  

Inhibitory effect of MS-275 on gastric glandular cancer cells and its possible mechanism

作　　者：王栋[1] 宫卫东[1] 黄辞[1] 李中华[1] 刘振堂[1] 吴智群[1] 

机构地区：[1]第四军医大学唐都医院介入科,西安710038

出　　处：《介入放射学杂志》2015年第4期333-337,共5页Journal of Interventional Radiology

基　　金：国家自然科学基金(30973464)

摘　　要：目的采用分子靶向药物治疗胃癌是近年研究热点。探讨组蛋白去乙酰化酶抑制因子MS-275通过多种途径选择性杀伤人胃低分化腺癌细胞株SGC-7901的机制。方法 10-100μmol/L药物浓度梯度的MS-275分别与SGC-7901、人正常胃黏膜上皮细胞株GES-1共培养24 h后,采用WST-1法检测SGC-7901及GES-1细胞存活率,流式细胞仪检测分析SGC-7901细胞线粒体膜电位变化,Western blot、实时荧光定量聚合酶链反应（RTQ-PCR）分别检测处理后胃癌细胞中p21、p27、p57、cyclin B1、cyclin D1基因及相应蛋白表达情况。结果 MS-275可使SGC-7901细胞存活率降低（P〈0.05）,其作用随药物浓度增大更明显,对GES-1细胞无显著影响;MS-275可降低SGC-7901细胞线粒体膜电位（P〈0.05）;MS-275显著提升p21、p27、p57基因及相应蛋白相对含量,同时降低cyclin B1、cyclin D1基因及其蛋白相对含量（P〈0.05）。结论 MS-275可选择性杀伤胃腺癌细胞SGC-7901,这一作用可能是通过线粒体凋亡途径及调控细胞周期相关基因和蛋白表达实现的。Objective The use of targeting therapy for the treatment of gastric glandular cancer has been a hot topic in recent years. This study aims to clarify that through what ways the histone deacetylase inhibitor MS-275 completes its selectively killing effect on gastric glandular cancer cell line SGC-7901. Methods SGC- 7901 cells and GES- 1 cells were respectively cultured for 24 h, with（10-100） μmol/L concentrations of MS- 275.（1） The survival rate of SGC- 7901 cells, GES- 1 cells and the normal cells were analyzed by WST-1;（2） The change of the mitochondrial membrane potential in SGC- 7901 was estimated by flow cytometry;（3） The expression levels of p21, p27, p57, cyclin B1, cyclin D1 were determined by Western blot and PCR methods. Results（1） MS- 275 could decrease the survival rate of SGC- 7901 cells, the effect was significantly enhanced with the increasing of the concentration（P〈0.05）, but MS- 275 showed no obvious effect on normal gastric mucosa epithelial cells GES- 1;（2） MS- 275 treatment could decreased the mitochondrial membrane potential of SGC- 7901 cells（P〈0.05）;（3） MS- 275 treatment could increase the relative contents of p21,p27, p57 genes and their protein and, at the same time, decrease the relative contents of Cyclin B1 and Cyclin D1（P〈0.05）. Conclusion MS- 275 treatment can selectively kill gastric glandular cancer cells SGC-7901 through several possible ways, such as inducing mitochondrial apoptosis and regulating the expression levels of cell cycle- related genes and proteins.

关 键 词：MS-275 胃腺癌 SGC-7901 线粒体凋亡 细胞周期阻滞 

分 类 号：R735.2[医药卫生—肿瘤]