DADS通过miR-222抑制人胃癌细胞系的增殖与侵袭  

Diallyl disulfide suppresses the proliferation and invasion of human gastric cancer cell line MGC-803 by down-regulating miR-222

作　　者：黄宁江[1] 刘乐江[1] 盘箐[1] 张志伟[2] 唐海林[2] 

机构地区：[1]永州职业技术学院药学系,湖南永州425000 [2]南华大学肿瘤研究所,湖南衡阳421001

出　　处：《基础医学与临床》2015年第12期1596-1600,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金(31100935);永州市科技计划项目[(2012)17号-22]

摘　　要：目的通过miRNA途径研究二烯丙基二硫(DADS)的抑瘤机制,以进一步阐明DADS抑制胃癌细胞增殖与转移的分子机制。方法将胃癌细胞系MGC-803细胞分为DADS处理组、miR-222模拟物组、miR-222抑制物组和阴性对照组;分别采用0、25、50、100、200和400μmol/L DADS处理MGC-803细胞;分别将miR-222模拟物、miR-222抑制物和scramble转染MGC-803细胞。qRT-PCR检测MGC-803细胞中miR-222表达;MTT法和Transwell侵袭实验检测MGC-803细胞增殖与侵袭能力;蛋白质印迹试验检测MGC-803细胞中TIMP3蛋白表达。结果 DADS可呈剂量依赖性下调MGC-803细胞中miR-222表达(P<0.05);DADS能抑制MGC-803细胞的增殖与侵袭,外源高表达miR-222能促进MGC-803细胞的增殖与侵袭,而miR-222抑制物与DADS共同处理,MGC-803细胞的增殖与侵袭抑制作用最为显著(P<0.05);DADS可下调MGC-803细胞中TIMP3蛋白的表达,外源高表达miR-222能上调MGC-803细胞中TIMP3蛋白的表达,而miR-222抑制物与DADS共同处理,MGC-803细胞中TIMP3蛋白的表达下调最为显著(P<0.05)。结论 DADS通过下调miR-222的表达,靶向TIMP3抑制胃癌细胞的增殖与侵袭。Objective To identify the mechanism related to miRNA pathway which plays a role in the anti-tumor effects of Diallyl disulfide. Methods Gastric cancer cell line MGC-803 was divided into DADS treatment group, miR- 222 mimics groups, miR-222 inhibitors group and negative control group ; MGC-803 cells were treated with 0, 25, 50, 100, 200,400 μmol/L DADS respectively; miR-222 mimics, miR-222 inhibitors and scramble sequence were transfected in MGC-803 cells respectively. A qRT-PCR was employed for detecting the expression of miR-222 in MGC-803 cells. Western blotting was conducted to detect the expressions of TIMP3 protein in MGC-803 cells. The proliferation and invasion ability of MGC-803 cells in vitro were evaluated by MTT and Transwell invasion as- says. Results miR-222 expression was down-regulated by increasing doses of DADS（P 〈 0.05） ; DADS could significantly inhibit MGC-803 cell proliferation and invasion capacity, ectopic expression of miR-222 could signifi- cantly promote MGC-803 cell proliferation and invasion capacity. Furthermore, gastric cancer cells treated with combination of DADS and miR-222 inhibitors showed significant inhibition to cell proliferation and invasion （ P 〈 0. 05 ） ; The expression of TIMP3 protein was inhibited by treatment with DADS in MGC-803 cells, overexpression of miR-222 resulted in increased TIMP3 protein levels. Furthermore, the expression of TIMP3 protein was inhibited as treated with combination of DADS and miR-222 inhibitors （P 〈 0.05 ）. Conclusions DADS suppresses prolifer- ation and invasion of human gastric cancer cells through targeting at TIMP3 by down-regulation of miR-222.

关 键 词：胃癌 MIR-222 二烯丙基二硫 增殖与侵袭 

分 类 号：R735.2[医药卫生—肿瘤]