Chm-1 Inhibits Hepatocyte Growth Factor-Induced Invasion of Sk-Hep-1 Human Hepatocellular Carcinoma Cells by Suppressing Matrix Metalloproteinase-9 Expression

Clinical observations suggest that hepatocyte growth factor( HGF) can promote invasion and metastasis in hepatocellular carcinoma. In this study , we found that HGF-stimulated invasion of SK-Hep-I cells, together with increased expression of matrix metalloproteinase (MMP)-9. CHM-1 was identified from 2-phenyl-4-quinolone derivatives to potently inhibit HGF- induced cell invasion, proteolytic activity, and expression of MMP-9. CHM- 1 significantly inhibited tyrosine autophosphorylation of c-Met induced by HGF. CHM- I also suppressed HGF-induced Akt phosphorylation, and NF- kappa B activation, the downstream regulators of HGF/c-Met signaling, resulting in the inhibition of MMP-9. Thus, we suggest that CHM-1 is a potential therapeutic agent against tumor invasion. (C) 2007 Elsevier Ireland Ltd. All rights reserved