VEGF基因沉默联合唑来膦酸抑制胃癌细胞增殖和迁移的机制  

Mechanisms of targeting VEGF gene combined with zoledronic acid on proliferation and migration of hepatocellular carcinoma cells

作　　者：李自显[1] 徐刚[2] 王亚楠[2] 杨文义 Li Zixian;Xu Gang;Wang Yanan;Yang Wenyi(Department of Digestive Medicine,Anyang District Hospital,Puyang City,Henan Anyang 455000,China;Department of Digestive Medicine,Second Affiliated Hospital of Zhengzhou University,Henan Zhengzhou 450000,China;Department of Digestive Medicine,First Affiliated Hospital of Henan University,Henan Kaifeng 475000,China)

机构地区：[1]濮阳市安阳地区医院消化内科,河南安阳455000 [2]郑州大学第二附属医院消化内科,河南郑州450000 [3]河南大学第一附属医院消化内科,河南开封475000

出　　处：《现代肿瘤医学》2019年第20期3597-3601,共5页Journal of Modern Oncology

基　　金：河南省教育厅科研基金项目(编号:16B320003)

摘　　要：目的:探讨靶向抑制VEGF基因联合唑来膦酸对胃癌细胞增殖、迁移及STAT3信号通路的影响。方法:采用LipofectamineTM2000将si-VEGF转染至胃癌BGC-823细胞中,以RT-PCR和Western blot检测其转染效果。转染后,加入不同浓度的唑来膦酸共同培养48 h,MTT法检测si-VEGF联合唑来膦酸对BGC-823细胞增殖的影响,并检测唑来膦酸的IC50;将细胞随机分为si-NC组(转染阴性对照)、si-NC+唑来膦酸组(转染阴性对照后,给予唑来膦酸处理)、si-VEGF组(转染si-VEGF)和si-VEGF+唑来膦酸组(转染si-VEGF后,给予唑来膦酸处理),Transwell小室实验检测细胞的侵袭和迁移能力,Western blot检测细胞中STAT3、p-STAT3和MMP-2蛋白的表达情况。结果:转染si-VEGF后成功下调BGC-823细胞中VEGF mRNA和蛋白的表达,si-VEGF联合唑来膦酸对BGC-823细胞增殖的抑制作用明显高于唑来膦酸单独作用,且唑来膦酸的IC50为62. 94μmol/L。与si-NC组相比,si-NC+唑来膦酸组、si-VEGF组和si-VEGF+唑来膦酸组的侵袭细胞数及迁移细胞数均明显减少,且p-STAT3和MMP-2蛋白表达明显降低,而STAT3表达差异不明显。其中,si-VEGF+唑来膦酸组的作用效果明显高于si-NC+唑来膦酸组或si-VEGF组。结论:靶向抑制VEGF基因联合唑来膦酸能够协调抑制胃癌细胞增殖和迁移,其作用机制可能与抑制STAT3信号通路有关。Objective:To investigate the effects of targeted inhibition of VEGF gene combined with zoledronic acid on proliferation,migration and STAT3 signaling in hepatocellular carcinoma cells.Methods:si-VEGF was transfected into BGC-823 cells by LipofectamineTM2000,and the transfection effects were detected by RT-PCR and Western blot.After transfection,different concentrations of zoledronic acid were used to co culture for 48 h.The effect of si-VEGF combined with zoledronic acid on the proliferation of BGC-823 cells was detected by MTT,and IC50 of zoledronic acid was detected.The cells were randomly divided into si-NC group(transfected negative control),si-NC+zoledronic acid group(after transfection of negative control,zoledronic acid treatment),si-VEGF group(transfected si-VEGF) and si-VEGF+zoledronic acid group(after transfection of si-VEGF,zoledronic acid treatment).The cell invasion and migration ability were detected by Transwell cell experiment,and the expression of STAT3,p-STAT3 and MMP-2 proteins in the cells were measured by Western blot.Results:After transfection of si-VEGF,the expression of VEGF mRNA and protein in BGC-823 cells was downregulated successfully.The inhibitory effect of si-VEGF combined with zoledronic acid on the proliferation of BGC-823 cells was significantly higher than that of zoledronic acid alone,and the IC50 of zoledronic acid was 62.94 μmol/L.Compared with the si-NC group,the numbers of invasive cells and migratory cells in the si-NC+zoledronic acid group,the si-VEGF group and the si-VEGF+zoledronic acid group were decreased obviously,and the expressions of p-STAT3 and MMP-2 protein were reduced obviously,but the differences of STAT3 expression were not obvious.Among them,the effect of si-VEGF+zoledronic acid group was significantly higher than that of si-NC+zoledronic acid group or si-VEGF group.Conclusion:The inhibition of VEGF gene and zoledronic acid can inhibit the proliferation and migration of hepatoma carcinoma cell,and the mechanism may be related to the inhibition of STAT3 sig

关 键 词：胃癌 VEGF基因 唑来膦酸 细胞增殖 STAT3信号通路 

分 类 号：R735.2[医药卫生—肿瘤]