γ-分泌酶抑制剂阻断LPA诱导的胃癌细胞SGC-7901侵袭迁移  

γ-secretase inhibitor block LPA-induced invasion and migration of SGC-7901 gastric cancer cells

作　　者：任志恒 张晨丽[1] 张晓 史淑霞 徐金宇 张煦[1] 胡燕 王斌生[3] REN Zhi-heng;ZHANG Chen-li;ZHANG Xiao;SHI Shu-xia;XU Jin-yu;ZHANG Xu;HU Yan;WANG Bin-sheng(Department of Pathology,College of Basic Medicine,Lanzhou University,Lanzhou 730030,China;Clinical Teaching and Research Group,Health College of Lanzhou Modern Vocational College,Lanzhou 730300,China;Department of General Surgery,the First Hospital of Lanzhou University,Lanzhou 730030,China)

机构地区：[1]兰州大学基础医学院病理学研究所,兰州730030 [2]兰州现代职业学院卫生分院临床教研组,兰州730300 [3]兰州大学第一医院普外科,兰州730030

出　　处：《临床与实验病理学杂志》2020年第1期15-19,共5页Chinese Journal of Clinical and Experimental Pathology

基　　金：甘肃省自然科学基金(1606RJDA313、18JR3RA293);兰州市科技计划(2017-4-64、2018-3-44);中央高校基本科研业务费专项资金(lzujbky-2017-123)

摘　　要：目的探讨γ-分泌酶抑制剂MK-0752阻断溶血磷脂酸(lysophosphatidic acid,LPA)诱导胃癌细胞SGC-7901的侵袭迁移。方法应用Western blot检测空白组、空白刺激组、实验组、实验刺激组细胞中LPA2、Notch1、Hes-1分子的表达;细胞侵袭迁移实验检测四组细胞的侵袭迁移情况;Western blot检测四组细胞上皮-间质转化(epithelial to mesenchymal transition,EMT)中相关蛋白表达;间接免疫荧光(immunofluorescence microscopy assay,IFA)观察四组细胞的形态学改变。结果实验组细胞LPA2、Notch1、Hes-1蛋白表达比空白组低,且侵袭迁移能力减弱;使用MK-0752预处理的SGC-7901细胞中E-cadherin表达比空白组高,vimentin表达比空白组低;细胞形态学结果表明:MK-0752可抑制LPA引起的SGC-7901细胞形态学改变。结论γ-分泌酶抑制剂可抑制由LPA诱导的胃癌细胞SGC-7901侵袭迁移,为胃癌的分子靶向治疗提供新的理论依据。Purpose To study the effect ofγ-secretase inhibitoRMK-0752 on the invasion and migration of gastric canceRcell line SGC-7901 induced by lysophosphatidic acid(LPA).Methods Western blot was used to detect the expression of LPA2,Notch1 and Hes-1 in the blank group,stimulation group,experimental group and experimental stimulation group.The change of invasion and migration of cells were tested by Transwell assay.Western blot was used to detect the expression of related proteins during the epithelial to mesenchymal transition(EMT)in fouRgroups of cells.Indirect immunofluorescence microscopy assay(IFA)was used to observe the morphological changes of the fouRgroups of cells.Results The expression of LPA2,Notch1 and Hes-1 in the experimental group were loweRthan that in the blank group,and the invasion and migration ability were weakened.The expression of E-cadherin in SGC-7901 cells which pretreated with MK-0752 was higheRthan that in the blank group,and vimentin was loweRthan that in the blank group.Cell morphology indicated MK-0752 inhibited the morphological changes of SGC-7901 cells induced by LPA.Conclusionγ-secretase inhibitoRinhibits invasion and migration of SGC-7901 gastric canceRthat is induced by LPA.It can provide a novel theoretical basis foRmoleculaRtargeted therapy of gastric canceRin the future.

关 键 词：胃肿瘤 LPA Γ-分泌酶抑制剂 侵袭 迁移 

分 类 号：R735.2[医药卫生—肿瘤]