Abstract: Objective Recent studies have shown that hepatic stellate cell in tumor microenviroment is an important regulator for hepatocellular carcinoma cell behavior. The aim of this study is to explore the impact of hepatic stellate cell in hepatocellular carcinoma invasion through SDF-1/CXCR4 axis. Methods The expressions of SDF-1 and CXCR4 were examined in hepatic stellate cell LX02, four hepatocellular carcinoma cell lines by Western blotting 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. Then, Western blotting was performed to evaluate the expression of epithelial mark E-Cadherin and mesenchymal mark 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 hepatic 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. Conclusion Hepatic stellate cells promote hepatocellular carcinoma cell invasion through chemokine SDF-1/CXCR4 axis, the mechanism may involve the epithelial-mesenchymal transition of carcinoma cell.

Key words: hepatocellular carcinoma, invasion, carcinoma, CXCR4, stellate cell.