姜黄素对缺氧诱导肝癌细胞HepG2上皮细胞间质转分化(EMT)的逆转作用  

Effect of Curcumin on epithelial-mesenchymal transition of hepatic cancer cell line HepG2 induced by hypoxia

作　　者：常远鸿[1] 江梅[1] 刘凯歌[2] 

机构地区：[1]西安市第四医院消化内科,陕西西安710004 [2]西安医学院附属医院消化内科,陕西西安710077

出　　处：《现代肿瘤医学》2012年第9期1763-1767,共5页Journal of Modern Oncology

基　　金：陕西省教育厅专项科研计划项目(No:11JK 0704)

摘　　要：目的:探讨姜黄素对缺氧诱导下人原发性肝癌细胞HepG2上皮细胞间质转分化的影响和可能机制。方法:将HepG2细胞分为3组:正常对照组、CoCl2组、CoCl2+姜黄素组。分组干预48小时后,四甲基偶氮唑盐(MTT)法检测细胞增殖能力,相差显微镜观察细胞形态变化,划痕试验检测细胞迁移能力,Real-time RT-PCR检测HIF1-αmRNA的表达变化,Western blot检测HIF1-α蛋白,上皮细胞表面标志E-Cadherin和间质细胞表面标志vimentin的变化。结果:分组干预48h,CoCl2组细胞增殖较对照组增高,而CoCl2+姜黄素组增殖较正常组降低;CoCl2组较正常对照组迁移能力显著增强,CoCl2+姜黄素组细胞迁移能力与CoCl2组相比明显下降;Real-time RT-PCR显示3组细胞HIF1-αmRNA的表达无明显差异;但是Western blot结果发现,相对于正常对照组,CoCl2组HIF1-α蛋白明显上调,CoCl2+姜黄素组HIF1-α蛋白变化不大;同时,CoCl2组E-cadherin表达水平下降而vimentin表达水平上升,CoCl2+姜黄素组无明显变化。结论:姜黄素可逆转缺氧诱导的肝癌细胞HepG2增殖和迁移能力增加,可能与其抑制缺氧诱导的HIF1-α蛋白上调和上皮细胞间质转分化有关。Objective：To investigate the effect of Curcumin on epithelial-mesenchymal transition in hepatocellu-lar cancer cell line HepG2 . Methods ： HepG2 cell was divided to 3 groups ： normal control group, CoC12 group, and CoC12 ＋ Curcumin group. After 48h of treatment, proliferation of cell was determined with methabenzthiazuron （MTF） assay. Migration of HepG2 was detected by wound healing assay. The mRNA expression of HIF - 1α was determined by real - time RT - PCR. The proteins of HIF - 1α, E - eadherin and vimentin were determined by Western blotting. Results：Compared with the normal control group, the proliferation of CoC12 group was significantly increased and CoC12 ＋ Curcumin group was decreased. Themigration of HepG2 cells were inhibited significantly by Curcumin com-pared with CoC12 group. The difference of mRNA expressions of HIF - 1α was not observed. Meanwhile, HIF - 1α was obviously up-regulated, E -cadherin was increased and vimentin was deceased at protein level in hypoxia induced by CoC12 which was abolished by Curcumin. Conclusion ： Curcumin abolished the up - regulation of proliferation and migration of HepG2 cell in hypoxia which induced by CoC12 , through decreased the expression of HIF - 1 α protein, and inhibited the epithelial - mesenchymal transition of HepG2.

关 键 词：肝细胞癌 侵袭 缺氧 上皮细胞间质转分化 姜黄素 

分 类 号：R73-361[医药卫生—肿瘤] R735.7[医药卫生—临床医学]