微粒体谷胱甘肽S转移酶1过度表达促进肝癌发生发展  

MGST1 overexpression promotes hepatocellular carcinoma development

作　　者：蔡培 黄富强 赵齐 周贤 杨华瑜[2] 毛一雷[2] 张宏冰[1] CAI Pei;HUANG Fu-qiang;ZHAO Qi;ZHOU Xian;YANG Hua-yu;MAO Yi-lei;ZHANG Hong-bing(Dept.of Physiology,Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC,Beijing 100005;Dept.of Liver Surgery,Peking Union Medical College Hospital,CAMS&PUMC,Beijing 100730,China)

机构地区：[1]中国医学科学院基础医学研究所北京协和医学院基础学院生理学系,北京100005 [2]中国医学科学院北京协和医学院北京协和医院肝脏外科,北京100730

出　　处：《基础医学与临床》2018年第7期950-956,共7页Basic and Clinical Medicine

基　　金：国家自然科学基金重点项目(81730078)

摘　　要：目的探讨微粒体谷胱甘肽S转移酶1(MGST1)在肝癌中的表达及其在肝癌细胞增殖、迁移和裸鼠成瘤中的作用。方法 Western blot检测人肝癌样品及肝癌细胞系中MGST1的表达;用慢病毒PLL3.7载体系统构建敲低MGST1的MHCC97H和HCCLM3细胞株及慢病毒p CDH载体系统构建过表达MGST1的SK-Hep-1细胞株后,用克隆形成实验检测细胞增殖能力;用Transwell实验检测细胞迁移能力;用皮下移植瘤实验检测MHCC97H细胞裸鼠成瘤能力。结果 71%(17/24)的肝癌组织中MGST1蛋白表达上调。敲低MGST1抑制MHCC97H和HCCLM3细胞的增殖、迁移能力(P<0.05);过表达MGST1促进SK-Hep-1细胞增殖、迁移(P<0.05);敲低MGST1的MHCC97H细胞裸鼠成瘤时间滞后(P<0.01),肿瘤体积减小(P<0.001),裸鼠生存期延长(P<0.001)。结论 MGST1过度表达促进肝癌发生发展,是治疗肝癌的一个新靶点。Objective To investigate the expression of microsomal glutathione S-transferase 1(MGST1)in hepatocellular carcinoma(HCC)and its significance in the development of HCC.Methods Western blot was used to measure MGST1 expression in human hepatocellular carcinoma and adjacent tissues and HCC cell lines.Furthermore,shRNA targeting MGST1 was constructed and transected into MHCC97H and HCCLM3 cells to deplete MGST1 expression.MGST1 was over-expressed in SK-Hep-1 cells using pCDH lentivirus system.Cell proliferation and migration were analyzed by colony formation and Transwell migration assay,respectively.The subcutaneous xenograft model of MHCC97H cells in nude mice was established to check tumor development and mouse survival.Results MGST1 was higher in 71%(17/24)of HCC tissues compared with their adjacent liver tissues.Cell proliferation and migration were significantly decreased by MGST1 knockdown,while they were increased by MGST1 overexpression.Furthermore,mice implanted with shMGST1 MHCC97H cells exhibited retarded tumor formation and tumor progression compared with control group.Conclusions MGST1 overexpression promotes hepatocellular carcinoma development and this molecule targeted for HCC treatment.

关 键 词：肝癌 MGST1 裸鼠 

分 类 号：R331[医药卫生—人体生理学]