微粒体谷胱甘肽S转移酶1过度表达促进肝癌发生发展

基础医学与临床 ›› 2018, Vol. 38 ›› Issue (7): 950-956.

微粒体谷胱甘肽S转移酶1过度表达促进肝癌发生发展

蔡培¹,黄富强¹,赵齐¹,周贤²,杨华瑜³,毛一雷⁴,张宏冰²

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
2. 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
3. 北京协和医院肝脏外科
4. 北京协和医院

收稿日期:2018-04-12 修回日期:2018-05-22 出版日期:2018-07-05 发布日期:2018-06-29
通讯作者: 张宏冰 E-mail:hbzhang@ibms.pumc.edu.cn
基金资助:
2017年国家自然科学基金重点项目

MGST1 overexpression promotes hepatocellular carcinoma development

Received:2018-04-12 Revised:2018-05-22 Online:2018-07-05 Published:2018-06-29
Contact: hongbing hongbingzhang E-mail:hbzhang@ibms.pumc.edu.cn

摘要/Abstract

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细胞系及慢病毒pCDH载体系统构建过表达MGST1的SK-Hep-1细胞系后，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。

关键词: 关键词：肝癌, MGST1, 裸鼠移植瘤

Abstract: 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 assay 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 (P<0.05). 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 can be targeted for HCC treatment.

Key words: Key words: hepatocellular carcinoma, MGST1, nude mice

中图分类号:

R331

蔡培黄富强赵齐周贤杨华瑜毛一雷张宏冰. 微粒体谷胱甘肽S转移酶1过度表达促进肝癌发生发展[J]. 基础医学与临床, 2018, 38(7): 950-956.