Hh信号通路特异性抑制剂环靶胺对胃癌细胞侵袭转移的影响及其机制探讨  

Effects of cyclopamine on invasion and migration of gastric cancer cells

作　　者：刘曼[1] 程玉[2] 田焕娜[2] 郝美玲[1] 李春辉[1] LIU Man;CHENG Yu;TIAN Huanna;HAO Meiling;LI Chunhui(The Affiliated Hospital of Chengde Medical University, Chengde 067000, China)

机构地区：[1]承德医学院附属医院,河北承德067000 [2]承德医学院

出　　处：《山东医药》2018年第2期17-20,共4页Shandong Medical Journal

基　　金：河北省医学科学研究重点课题项目(ZL20140103);河北省政府资助临床优秀人才基金资助项目

摘　　要：目的观察Hedgehog(Hh)信号通路特异性抑制剂环靶胺对人胃癌细胞侵袭转移的影响,并探讨其机制。方法用不同浓度的环靶胺处理人胃癌细胞MGC-803,MTT法检测细胞的增殖能力,Transwell小室观察细胞的迁移、侵袭等转移能力,qRT-PCR法检测Hh信通路相关蛋白Smo、Gli-1和转移相关因子基质金属蛋白酶9(MMP-9)mRNA表达,Western blotting法检测Gli-1、MMP-9蛋白表达。结果随着环靶胺浓度的增加和作用时间的延长,胃癌细胞增殖抑制率逐渐增加(P均<0.05);环靶胺处理胃癌细胞24 h,40μmol/L处理的细胞侵袭和转移的穿膜细胞数均少于0μmol/L(P均<0.05),40μmol/L处理的细胞Gli-1、Smo、MMP-9 mRNA相对表达量均低于0μmol/L(P均<0.05),40μmol/L处理的细胞Gli-1、MMP-9蛋白相对表达量均低于0μmol/L(P均<0.05)。结论环靶胺能通过抑制Hh信号通路下调MMP-9表达,从而抑制胃癌细胞MGC-803的侵袭和转移。Objective To investigate the effects of Hedgehog（Hh） signaling pathway specific inhibitor cyclopamine on the migration and invasion of gastric cancer cells MGC-803,and to explore its possible mechanism.Methods Different concentrations of cyclopamine were given to MGC-803 cells.The cell proliferation ability was measured by MTT,and the cell invasion and migration abilities were detected by Transwell assay.The mRNA expression of Smo,Gli-1,and MMP-9 was detected by qRT-PCR.The protein expression of Gli-1 and matrix metalloproteinase 9（MMP-9） was detected by Western blotting.Results With the increased concentrations of cyclopamine and the treatment time,the proliferation inhibition rate of gastric cancer cells gradually increased（P 〈 0.05）.At 24 h after treatment,the transmembrane cells of invasion and metastasis treated with 40 μmol/L cyclopamine were less than that treated with 0 μmol/L（all P 〈 0.05）.The relative mRNA expression of Gli-1,Smo,and MMP-9 in cells treated with 40 μmol/L cyclopamine was lower than that treated with0 μmol/L（all P 〈 0.05）.The relative expression of Gli-1 and MMP-9 in cells treated with 40 μmol/L cyclopamine was lower than that treated with 0 μmol/L（all P 〈 0.05）.Conclusion Cyclopamine can inhibit the invasion and migration abilities of MGC-803 cells by inhibiting the Hedgehog signaling pathway and down-regulating the expression of MMP-9.

关 键 词：胃癌 环靶胺 HEDGEHOG信号通路 Smo基因 Gli-1基因 基质金属蛋白酶 细胞增殖 细胞侵袭 细胞转移 

分 类 号：R735.2[医药卫生—肿瘤]