AGGF1促进肝癌细胞血管生成作用及机制的研究  

Study on AGGF1 promoting angiogenesis in liver cancer cells and its mechanism

作　　者：刘少平[1,2,3] 卫银芝 胡亚华[4] 张海[4] 赵俊 LIU Shaoping;WEI Yinzhi;HU Yahua;ZHANG Hai;ZHAO Jun(Department of General Practice,Huangshi Central Hospital,Affiliated Hospital of Hubei Polytchnic University,Huangshi 435000;The First Clinical Medical College of Hubei Polytchnic University;Hubei Provincial Key Laboratory of the Occurrence and Intervention of Renal Diseases;Department of Gastroenterology,Huangshi Central Hospital,Affiliated Hospital of Hubei Polytchnic University,China)

机构地区：[1]黄石市中心医院(湖北理工学院附属医院)全科医学科,湖北黄石435000 [2]湖北理工学院第一临床学院 [3]肾脏疾病发生与干预湖北省重点实验室 [4]黄石市中心医院(湖北理工学院附属医院)消化内科

出　　处：《胃肠病学和肝病学杂志》2025年第2期195-198,共4页Chinese Journal of Gastroenterology and Hepatology

基　　金：湖北省自然科学基金创新发展联合基金(2022CFD067);湖北理工学院校级科研项目(22xjz05Y)。

摘　　要：目的研究G-patch和FHA结构域1血管生成因子(angiogenic factor with G-patch and FHA domain 1,AGGF1)促进肝癌细胞血管生成的作用及其机制。方法构建HepG2肝癌细胞与人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVEC/EC)共培养体系,分Lv-control+EC,Lv-AGGF1+EC,Sh-control+EC和Sh-AGGF1+EC四组,观察稳定过表达和敲减AGGF1的HepG2细胞分别对EC迁移和小管形成能力的影响,加入VEGFA中和抗体后再次观察Lv-AGGF1+EC组EC迁移和小管形成能力的变化;ELISA检测上清VEGFA含量;Western blotting检测HepG2细胞中ERK信号通路相关因子表达。结果与对照组比较,Lv-AGGF1+EC组VEGFA含量显著升高,EC跨膜数显著增多、管腔形成能力显著增强,加入VEGFA中和抗体后EC跨膜数明显减少、管腔形成能力也明显减弱。与对照组比较,Sh-AGGF1+EC组VEGFA含量明显减少,EC跨膜数明显减少、管腔形成能力也明显减弱。过表达AGGF1的HepG2细胞中ERK磷酸化水平(ERK phosphorylation,p-ERK)明显升高,缺氧诱导因子-1ɑ(hypoxia inducible factor-1ɑ,HIF-1ɑ)和VEGFA的表达上调,而敲减AGGF1后p-ERK明显下降,HIF-1ɑ和VEGFA的表达也下调。结论AGGF1通过激活ERK/HIF-1ɑ通路,上调VEGFA表达,从而促进肝癌血管生成。Objective To investigate the role and mechanism of angiogenic factor with G-patch and FHA domain 1(AGGF1)promoting angiogenesis in liver cancer cells.Methods A co-culture system of HepG2 cells and human umbilical vein endothelial cells(HUVEC/EC)was constructed,divided into 4 groups:Lv-control+EC,Lv-AGGGF1+EC,Sh-control+EC and Sh-AGGGF1+EC.The effects of stable overexpression and knockdown of AGGF1 on EC migration and tube formation was observed,and VEGFA neutralizing antibody was added to the Lv-AGGGF1+EC group,observed its effects on the migration and tube formation ability of EC.The content of VEGFA in the supernatant was detected by ELISA.The expression of ERK signaling pathway related factors in HepG2 cells were detected by Western blotting.Results Compared with the control group,the VEGFA content,the number of transmembrane EC,tube formation ability of EC in Lv-AGGGF1+EC group were significantly increased.After adding VEGFA neutralizing antibody,the number of transmembrane EC,tube formation ability of EC were obviously decreased.Compared with the control group,the VEGFA content,the number of transmembrane EC,tube formation ability of EC in Sh-AGGGF1+EC group were significantly reduced.ERK phosphorylation(p-ERK)levels significantly increased in HepG2 cells with overexpressing AGGF1,while expression of HIF-1ɑand VEGFA were upregulated and knockdown of AGGF1 resulted in a significant decrease in p-ERK levels and expression of HIF-1ɑand VEGFA.Conclusion AGGF1 activate ERK/HIF-1ɑpathway,upregulate VEGFA expression,thereby promote angiogenesis in liver cancer.

关 键 词：AGGF1 血管生成 肝癌 ERK VEGFA 

分 类 号：R735.7[医药卫生—肿瘤]