细胞外HSP70/HSP70-PCs对人肝癌HepG2细胞上皮-间充质转化的影响及机制研究  

Effect of extracellular HSP70 /HSP70-PCs on epithelial-mesenchymal transition of human hepatocellular carcinoma HepG2 cells

作　　者：李航宇[1] 李岩[1] 刘丹[1] 孙宏治[2] 刘金钢[1] 

机构地区：[1]中国医科大学附属盛京医院普通外科,辽宁沈阳110004 [2]辽宁医学院附属第一医院普通外科,辽宁锦州121001

出　　处：《中国病理生理杂志》2013年第9期1631-1636,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81071955);辽宁省教育厅科技项目计划(No.L2010634)

摘　　要：目的:探讨细胞外热休克蛋白70(HSP70)/HSP70肽复合物(HSP70-PCs)对肝癌细胞上皮-间充质转化(EMT)的影响和可能机制。方法:将HepG2细胞分为3组:正常对照组、HSP70/HSP70-PCs组(终浓度2mg/L)和LY294002+HSP70/HSP70-PCs组。应用real-time RT-PCR与Western blotting法检测上皮细胞表面标志Ecadherin和间质细胞表面标志α-平滑肌肌动蛋白(α-SMA)的表达变化,以及磷脂酰肌醇3-激酶(PI3K)和缺氧诱导因子1α(HIF1-α)的表达变化。结果:细胞外HSP70/HSP70-PCs可以促进HepG2细胞EMT的发生。HepG2细胞的EMT过程伴随HIF-1α和PI3K表达增加。应用LY294002阻断PI3K后,HepG2细胞没有发生EMT,同时细胞外HSP70/HSP70-PCs上调HIF-1α表达的作用消失。结论:细胞外HSP70/HSP70-PCs可以通过PI3K/HIF-1α促进肝癌细胞发生EMT。AIM：To investigate the effect of extracellular heat-shock protein 70 （HSP70）/HSP70-peptide complexes （HSP70-PCs） on epithelial-mesenchymal transition （EMT） of human hepatocellular carcinoma HepG2 cells and its probable mechanism. METHODS：HepG2 cells were divided into 3 groups： control group, HSP70/HSP70-PCs （2 mg/L） group and LY294002＋HSP70/HSP70-PCs group. The mRNA and protein expression of epithelial cell surface marker E-cadherin, mesenchymal cell surface marker α-smooth muscle actin （α-SMA）, phosphatidylinositol 3-kinase （PI3K） and hypoxia-inducible factor 1α （HIF-1α） was examined by real-time RT-PCR and Western blotting. RESULTS：Extracellular HSP70/HSP70-PCs promoted the initiation of EMT of HepG2 cells. The expression of HIF-1α and PI3K significantly increased in the process of EMT of HepG2 cells. After PI3K was blocked by LY294002, EMT did not occur and HIF-1α was not up-regulated in HepG2 cells. CONCLUSION：Extracellular HSP70/HSP70-PCs may promote EMT of hepatocellular carcinoma cells via PI3K/HIF-1α signaling pathway.

关 键 词：上皮-间充质转化 HEPG2细胞 热休克蛋白70 

分 类 号：R735.7[医药卫生—肿瘤]