DADS上调RORα抑制人胃癌MGC803细胞增殖与迁移侵袭  

Up-regulation of RORα Induced by Diallyl Disulfide Inhibiting Proliferaion,Migration and Invasion of Human Gastric Cancer MGC803 Cells

作　　者：苏波[1,2] 向姝霖[2,3] 苏坚[2,4] 赵晓红[2,5] 夏红[2] 刘芳[2] 凌晖[2] 苏琦[2] 

机构地区：[1]南华大学药学与药理学研究所,湖南省高校药物蛋白质组学重点实验室,湖南衡阳421001 [2]南华大学肿瘤研究所,湖南省胃癌研究中心、湖南省高校肿瘤细胞与分子病理学重点实验室 [3]南华大学附属怀化医院、怀化市第一人民医院 [4]南华大学附属第二医院病理科 [5]海南省妇幼保健院

出　　处：《中南医学科学杂志》2016年第6期604-609,共6页Medical Science Journal of Central South China

基　　金：国家自然科学基金(81374013,81102854);湖南省卫计委科研课题(B2015-182)

摘　　要：目的研究二烯丙基二硫(DADS)是否通过上调维甲酸相关孤核受体α(RORα)表达抑制人胃癌MGC803细胞增殖、细胞周期与迁移侵袭。方法实验组分为6组,对照组,空载体组,RORα干扰组(miRRORα),DADS组,空载体联合DADS组,miR-RORα联合DADS组。Western blot检测RORα、MMP-9与TIMP3蛋白表达。MTT、流式细胞术、迁移和侵袭实验分别检测细胞增殖、细胞周期与迁移侵袭的改变。结果 DADS处理细胞24 h后,与对照组和空载体组比较,DADS上调RORα和TIMP3、下调MMP-9蛋白表达。干扰组较对照组与空载体组RORα表达明显下调。与DADS处理组比较,干扰RORα表达上调MMP-9、下调TIMP3蛋白表达。MTT实验显示,DADS抑制MGC803细胞增殖,而干扰RORα表达促进增殖。流式细胞术显示,DADS诱导G2/M期阻滞,下调RORα削弱其作用。迁移实验显示,DADS处理组迁移距离明显减少。RORα干扰组迁移距离明显高于对照组和空载体组。侵袭实验显示,DADS处理组较对照组和空载体组穿膜细胞明显减少。干扰组穿膜细胞明显多于对照组和空载体组。干扰RORα表达降低DADS对细胞迁移和侵袭的抑制作用。结论 DADS上调TIMP3表达,下调MMP-9表达,抑制MGC803细胞增殖与迁移侵袭,其作用机制与上调RORα表达有关。Objective To investigate whether diallyl disulfide （DADS） inhibits human gastric cancer MGC803 cell proliferation, migration and invasion by up-regulating the expression of RORα. Methods The experimental group was divided into six groups, control group, vector group, DADS group, vector＋DADS group, and miR-RORα＋DADS group. RORα, miR-RORα, MMP-9 and TIMP3 protein levels were detected by using Western blot. MTF and flow cytometry were used for cell proliferation and cell cycle assays.Wound healing and transweU assays were performed to examine cell migration and invasion activities. Results DADS increased RORα and TIMP3 expression, decreased MMP-9 expression. TIMP3 was down-regulated and MMP-9 was up-regulated in miR-RORα stable expression cells.DADS induced cell proliferation inhibition and cell cycle G2/M phase arrest.Downregulation of RORα by miR attenuated these effects of DADS.Compared with control and vector groups, the migration distance was decreased and increased in DADS treated and miR-RORα expression groups,respectively.And,the mumber of cancer cells which passed through the Matrigel coated membrane was reduced and increased in DADS treated and miR-RORα expression groups, respectively.miR-RORα attenuated the inhibitory effects of DADS on cell migration and invasion. Conclusions DADS can increase TIMP3 and decrease MMP-9 expression, suppressing proliferation, migration and invasion of human gastric cancer MGCS03 cells, and its mechanism may be associated with up-regulating RORα.

关 键 词：二烯丙基二硫 RORα 人胃癌细胞 增殖 迁移与侵袭 

分 类 号：R735.2[医药卫生—肿瘤]