姜黄素对缺氧诱导的人原发性肝癌细胞HepG2上皮细胞间充质转化的影响  

Curcumin Inhibited Hypoxia Induced Epithelial-Mesenchymal Transition in Hepatic Carcinoma Cell Line HepG2 in vitro

作　　者：常远鸿[1] 江梅[1] 刘凯歌[2] 李徐奇[3] 

机构地区：[1]西安市第四医院消化内科,西安710004 [2]西安医学院附属医院消化内科,西安710007 [3]西安交通大学医学院第一附属医院普通外科,西安710061

出　　处：《中国中西医结合杂志》2013年第8期1102-1106,共5页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：陕西省教育厅专项科研计划资助项目(No.11JK0704)

摘　　要：目的探讨姜黄素对缺氧诱导下人原发性肝癌细胞HepG2上皮细胞间充质转化的影响及其可能机制。方法将HepG2细胞分3组:正常对照组、氯化钴(CoCl2)组和CoCl2加10μmol/L姜黄素组。采用MTT法检测细胞增殖能力,划痕实验检测细胞迁移能力,Real-timeRT-PCR检测缺氧诱导因子-1α(hy-poxia-induciblefactor-1α,HIF-1α)mRNA表达,Westernblot检测HIF-1α蛋白、E-钙黏蛋白(epithelial-cadher-in,E-cadherin)、波形蛋白(Vimentin)表达。结果 HepG2细胞被CoCl2诱导缺氧后,细胞增殖及迁移能力增强,HIF-1α蛋白表达上调,上皮标志蛋白E-cadherin表达下降而间质标志蛋白Vimentin表达上调,与正常对照组比较,差异均有统计学意义(P<0.05)。姜黄素干预缺氧HepG2细胞后,其增殖与迁移能力被明显抑制,同时HIF-1α蛋白表达下降,E-cadherin蛋白表达上调,Vimentin蛋白表达下降,与CoCl2组比较,差异均有统计学意义(P<0.05)。3组HIF-1αmRNA表达比较,差异无统计学意义(P>0.05)。结论缺氧诱导肝癌细胞HepG2增殖和迁移能力的增强可被姜黄素逆转,可能与姜黄素抑制缺氧诱导的HIF-1α蛋白上调和上皮细胞间充质转化有关。Objective To explore effects and possible mechanisms of curcumin on hypoxia induced epithelial-mesenchymal transition （ EMT） in hepatocellular carcinoma cell line HepG2. Methods HepG2 cells were divided to 3 groups, i.e., the normal control group, the CoCI2 group, and the CoCI2 plus 10 μmol/L curcu- rain group. The proliferation of HepG2 was determined using MI-F assay. The migration of HepG2 was detected by wound healing assay. The mRNA expression of hypoxia-inducible factor-1 （HIF-1α） was evaluated with real- time RT-PCR. The protein expressions of HIF-1α, epithelial-cadherin （E-cadherin）, and vimentin were deter- mined using Western blot. Results Compared with the normal control group, the proliferation and migration of HepG2 cells under CoC12-induced hypoxia significantly increased, the expression of HIF-1α was up-regulated, and the expression of E-cadherin protein was obviously down-regulated, and the expression of vimentin signifi- cantly increased （（all P 〈0. 05）. Intervention by curcumin significantly inhibited the proliferation and migration of hypoxic HepG2 cells, and expressions of HIF-lcx and vimentin decreased, and the expression of E-cadherin was up-regulated, showing statistical difference when compared with those of the CoCI2 group （P 〈 0.05）. There was no statistical difference in HIF-lcx mRNA expression among the 3 groups （P 〉0.05）. Conclusion Curcumin could reverse the proliferation and migration of HepG2 cells under CoCI2-induced hypoxia condition, which might be associated with inhibiting up-regulated expressions of HIF-1α protein and EMT.

关 键 词：肝癌细胞 侵袭 缺氧 上皮细胞间充质转化 姜黄素 

分 类 号：R735.7[医药卫生—肿瘤] R285.5[医药卫生—临床医学]