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-kappaB 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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology*
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Cell Line, Tumor
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Dioxoles / chemical synthesis*
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Dioxoles / pharmacology*
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Gene Expression Regulation, Neoplastic*
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Hepatocyte Growth Factor / metabolism
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Humans
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I-kappa B Kinase / metabolism
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 9 / metabolism
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Models, Biological
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Models, Chemical
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NF-kappa B / metabolism
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Neoplasm Invasiveness
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Neoplasm Metastasis
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Phosphorylation
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Quinolones / chemical synthesis*
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Quinolones / pharmacology*
Substances
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2'-fluoro-6,7-methylenedioxy-2-phenyl-4-quinolone
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Antineoplastic Agents
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Dioxoles
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NF-kappa B
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Quinolones
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Hepatocyte Growth Factor
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I-kappa B Kinase
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9