CHM-1 inhibits hepatocyte growth factor-induced invasion of SK-Hep-1 human hepatocellular carcinoma cells by suppressing matrix metalloproteinase-9 expression

Shih Wei Wang, Shiow Lin Pan, Chieh Yu Peng, Der Yi Huang, An Chi Tsai, Ya Ling Chang, Jih Hwa Guh, Sheng Chu Kuo, Kuo Hsiung Lee, Che Ming Teng

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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-1 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-1 also suppressed HGF-induced Akt phosphorylation, and NF-κB 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.

Original languageEnglish
Pages (from-to)87-96
Number of pages10
JournalCancer Letters
Volume257
Issue number1
DOIs
Publication statusPublished - Nov 8 2007
Externally publishedYes

Keywords

  • Hepatocellular carcinoma
  • HGF
  • Invasion
  • MMP-9

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

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