表皮生长因子蛛毒素受体7次跨膜结构域1通过血管内皮生长因子信号通路调控胃癌迁移的机制研究  

Study on the mechanism of ADGRL4 regulating gastric cancer metastasis through vascular endothelial growth factor signaling pathway

作　　者：罗庆伟[1] 李志红[1] 汤俊[1] 周志军 严伟[1] 江旭林 陈校力 胡刚强[1] LUO Qingwei;LI Zhihong;TANG Jun;ZHOU Zhijun;YAN Wei;JIANG Xulin;CHEN Xiaoli;HU Gangqiang(Gastrointestinal Surgery of Ezhou Central Hospital,Ezhou 436099,China)

机构地区：[1]鄂州市中心医院胃肠外科,湖北鄂州436099

出　　处：《中国肿瘤外科杂志》2024年第4期382-387,共6页Chinese Journal of Surgical Oncology

基　　金：鄂州市科技局基础及人才创新专项(EZ01⁃007⁃20220006)。

摘　　要：目的探究表皮生长因子蛛毒素受体7次跨膜结构域1(ADGRL4)通过血管内皮生长因子(VEGF)信号通路调控胃癌迁移的机制。方法将正常胃黏膜上皮细胞GES⁃1、胃癌细胞SGC⁃7901、HGC⁃27、Hs⁃746T传代培养后,检测ADGRL4表达量。将胃癌SGC⁃7901细胞分为对照组、过表达组、沉默组。对照组转染空载体,过表达组转染ADGRL4上调质粒,沉默组转染ADGRL4沉默质粒。分析并比较3组胃癌细胞侵袭、迁移数及VEGF信号通路蛋白表达量。结果与正常胃黏膜上皮细胞GES⁃1比较,胃癌细胞SGC⁃7901、HGC⁃27、Hs⁃746T中ADGRL4表达量均上升(P<0.05);与胃癌细胞HGC⁃27、Hs⁃746T比较,胃癌细胞SGC⁃7901中ADGRL4表达量较高(P<0.05),故选择SGC⁃7901进行后续实验。与对照组比较,过表达组ADGRL4表达量上升,沉默组ADGRL4表达量下降(P<0.05);与过表达组比较,沉默组ADGRL4表达量下降(P<0.05),说明ADGRL4转染成功。与对照组比较,过表达组细胞侵袭数、迁移数、基质金属蛋白酶(MMP)⁃2、MMP⁃9、VEGF、血管内皮生长因子受体⁃2(VEGFR⁃2)表达量上升,E⁃钙黏蛋白(E⁃cadherin)表达量下降,沉默组细胞侵袭数、迁移数、MMP⁃2、MMP⁃9、VEGF、VEGFR⁃2表达量下降,E⁃cadherin表达量上升(P<0.05);与过表达组比较,沉默组细胞侵袭数、迁移数、MMP⁃2、MMP⁃9、VEGF、VEGFR⁃2表达量下降,E⁃cadherin表达量上升(P<0.05)。结论胃癌细胞经下调ADGRL4干预后,侵袭、迁移数减少,迁移、侵袭相关蛋白表达量得到调节,其机制可能与VEGF通路受到抑制有关。Objective To explore the mechanism of EGF spider toxin receptor 7th transmembrane domain 1(ADGRL4)regulating gastric cancer metastasis through vascular endothelial growth factor(VEGF)signaling pathway.Methods ADGRL4 expression was detected in normal gastric mucosal epithelial cells and gastric cancer cells after culture.Gastric cancer SGC⁃7901 cells were divided into control group,overexpression group and silence group.The control group was transfected with empty vector,the overexpression group was transfected with ADGRL4 up⁃regulated plasmid,and the silent group was transfected with ADGRL4 silent plasmid.To analyze the effects of regulating ADGRL4 expression on invasion,migrate and VEGF signaling pathway protein expression of gastric cancer cells.Results Compared with normal gastric mucosal epithelial cells GES⁃1,the expression of ADGRL4 in gastric cancer cells SGC⁃7901,HGC⁃27 and Hs⁃746T was increased(P<0.05).Compared with gastric cancer cells HGC⁃27 and Hs⁃746T,the expression level of ADGRL4 in gastric cancer cells SGC⁃7901 was higher(P<0.05),so SGC⁃7901 was selected for follow⁃up experiment.Compared with the control group,the expression level of ADGRL4 was increased in overexpression group and decreased in silence group(P<0.05).Compared with the overexpression group,the expression level of ADGRL4 in the silent group was decreased(P<0.05),indicating successful transfection of ADGRL4.compared with the control group,the invasion number,migrate number,matrix metalloproteinase(MMP)⁃2,MMP⁃9,VEGF,vascular endothelial growth factor receptor⁃2(VEGFR⁃2)expression of cells in overexpression group increased,while the expression of E⁃cadherin decreased.The invasion number,migrate number,the expression levels of MMP⁃2,MMP⁃9,VEGF and VEGFR⁃2 decreased in the silent group,while the expression level of E⁃cadherin increased(P<0.05).Compared with the overexpression group,the invasion number,migrate number,the expressions of MMP⁃2,MMP⁃9,VEGF and VEGFR⁃2 in the silent group were decre

关 键 词：表皮生长因子蛛毒素受体7次跨膜结构域1 血管内皮生长因子 胃癌 迁移 

分 类 号：R735.2[医药卫生—肿瘤]