肝星状细胞通过SDF-1/CXCR4轴诱导肝癌细胞上皮间质转分化并促进其侵袭  

Hepatic stellate cell through SDF-1/CXCR4 axis induces epithelial-mesenchymal transition in hepatocellular carcinoma invasion

作　　者：李四光[1] 常远鸿[2] 刘凯歌[3] 

机构地区：[1]西安医学院临床医学院,陕西西安710021 [2]西安市第四医院消化内科,陕西西安710004 [3]西安医学院附属医院消化内科,陕西西安710077

出　　处：《基础医学与临床》2013年第8期998-1003,共6页Basic and Clinical Medicine

基　　金：陕西省教育厅专项科研计划项目(11JK 0704)

摘　　要：目的探讨肝星状细胞是否通过SDF-1/CXCR4轴促进肝癌细胞侵袭的作用和可能机制。方法通过Westernblot和real time RT-PCR,检测肝星状细胞LX02和肝癌细胞系SDF-1、CXCR4表达。Transwell实验检测星状细胞LX02或外源性SDF-1干预对肝癌细胞HepG2以及CXCR4基因沉默后的HepG2侵袭的影响,Western blot检测上皮标志E-cadherin和间质标志vimentin的表达变化。结果肝星状细胞LX02中趋化因子SDF-1高表达,4株人肝细胞癌细胞系均有CXCR4高表达,其中HepG2细胞表达最强。星状细胞或SDF-1均能诱导肝癌细胞上皮-间质分化并促进其侵袭。通过RNA干扰技术靶向沉默肝癌细胞CXCR4基因,星状细胞或SDF-1均不能增强其细胞侵袭能力,不能诱导肝癌细胞HepG2发生上皮-间质分化。结论肝星状细胞通过趋化因子SDF-1/CXCR4轴促进肝癌细胞侵袭,其机制可能与诱导肝癌上皮-间质转化有关。Objective The aim of this study is to explore the impact of hepatic stellate cell in hepatocellular carci- noma invasion through SDF-1/CXCR4 axis. Methods The expression of SDF-1 and CXCR4 were examined in he- patic stellate cell LX02, four hepatocellular carcinoma cell lines by Western blot at protein levels and real-time RT- PCR at mRNA level respectively. In addition, Transwell invasion assay was carried out to analyze the influence of hepatic stellate cell LX02 and SDF-1 on invasion of hepatocellular carcinoma cell HepG2 under normal condition or CXCR4 gene silence condition. Western blot was performed to evaluate the expression of epithelial marker E-cad- herin and mesenchymal marker vimentin. Results The expression of SDF-1 was high in hepatic stellate cell LX02, and increased levels of expression of CXCR4 were found in all hepatocellular carcinoma cells. Co-culture with he- patic stellate cell LX02 or treatment with SDF-1 both induced the epithelial-mesenchymal transition and increased the invasion of hepatocellular carcinoma cell HepG2. Furthermore, inhibition of CXCR4 by gene silence in HepG2 suppressed the enhanced invasion and epithelial-mesenchymal transition of HepG2 cells which induced by stellate cells or SDF-1. Conclusions Hepatic stellate cells promote hepatoeellular carcinoma cell invasion through chemo- kine SDF-1/CXCR4 axis, the mechanism may involve the epithelial-mesenchymal transition of carcinoma cell.

关 键 词：肝癌 侵袭 肿瘤 CXCR4 肝星状细胞 

分 类 号：R735.7[医药卫生—肿瘤]