表没食子儿茶素没食子酸酯对缺氧诱导的肝细胞癌HepG2细胞HIF-1α及VEGF蛋白表达的影响  

Effect of (-)-epigallocatechin-3-gallate on hypoxia-induced expression of HIF-1_α and VEGF protein in HepG2 cells

作　　者：王熙[1] 谢纪文 刘礼[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院中西医结合科,湖北省武汉市430022

出　　处：《世界华人消化杂志》2009年第4期357-361,共5页World Chinese Journal of Digestology

基　　金：湖北省卫生厅中医药;中西医结合科研课题基金资助项目;No.200389~~

摘　　要：目的:探讨表没食子儿茶素没食子酸酯[(-)-epigallocatechin-3-gallate,EGCG)]对缺氧诱导的肝细胞癌HepG2细胞HIF-1α及VEGF表达的影响.方法:在缺氧条件体外培养肝细胞癌HepG2细胞16h,并以不同浓度EGCG处理,即低剂量(10μmol/L)、中剂量(50μmol/L)、高剂量(100μmol/L),制成细胞爬片以免疫组化SABC法检测HIF-1α及VEGF表达的变化,同时设常氧组及缺氧对照组进行比较.结果:常氧状态下HepG2细胞中HIF-1α几乎无表达,VEGF有少量表达.缺氧对照组经16h缺氧后HIF-1α表达明显上调,与常氧组相比有显著差异(t=3.579,P<0.01);VEGF表达亦较常氧组明显上调,两者有明显差异(t=6.372,P<0.01).同浓度的EGCG对缺氧各组细胞HIF-1α及VEGF表达,与缺氧对照组相比均有不同明显抑制作用(HIF:F=56.818,P<0.05;VEGF:F=10.016,P<0.05),EGCG对HIF-1α及VEGF表达的抑制作用呈剂量依赖性,且相关分析显示,HIF-1α及VEGF蛋白表达同步化(r=0.617,P<0.05).结论:EGCG可从蛋白水平下调缺氧诱导的HepG2细胞HIF-1α及VEGF的表达水平,从而有可能抑制肿瘤血管新生.AIM： To explore the effect of （-）-epigallocatechin- 3-gallate （EGCG） on hypoxia-induced expression of hypoxia inducible factor I alpha （HIF-1α） and vascular endothelial growth factor （VEGF） in human hepatoma line HepG2 cells. METHODS： The human hepatoma line HepG2 cells were cultured under hypoxic conditions in vitro. The cultured cells were treated with different concentrations of EGCG for 16 h in the 6-well dish with coverslips. The expression of HIF-1α and VEGF proteins were determined by immunohistochemical staining. HepG2 cells were also cultured in normal oxygen condition as normal control group and in hypoxic condition without EGCG as hypoxia control group. RESULTS： Under normal condition, there was almost no HIF-1α protein expression and weak VEGF protein expression in HepG2 cells. Hypoxia significantly induced up-regulation of the expression of both HIF-la and VEGF （t = 3.579, P 〈 0.01; t = 6.372, P 〈 0.01, respectively）. Compared with hypoxia control group, marked inhibitory effect on both HIF-1α and VEGF expression in all hypoxia groups was observed by EGCG at a definite concentration （HIF： F = 56.818, P 〈 0.05; VEGF： F = 10.016, P 〈 0.05）. The inhibition by EGCG on HIF-1α and VEGF expression showed a dose-dependent relationship. Additionally, correlation analysis showed that HIF-1α expression synchronized with VEGF expression （r = 0.617, P 〈 0.05）. CONCLUSION： EGCG has significant inhibitory effects on the protein expression of HIF-1α and VEGF induced by hypoxia in a dose-dependent manner.

关 键 词：表没食子儿茶素没食子酸酯 HEPG2细胞 缺氧诱导因子1-Α 血管内皮生长因子 血管新生 

分 类 号：R735.7[医药卫生—肿瘤]