Abstract
c-Met, a type of receptor tyrosine kinase, may be significantly associated with the progression of hepatocellular carcinoma (HCC). In addition, des-γ-carboxyprothrombin (DCP) has been found to interact with c-Met and activate HCC cell growth. Therefore, the functional inhibition of c-Met expressed on HCC cells should arrest HCC cell growth. The present study found that the c-Met inhibitor SU11274 suppressed HCC cell growth by inhibiting the activation of c-Met. Furthermore, this inhibitor also neutralized the activation of HCC cell growth resulting from the addition of DCP. These results suggest that the functional inhibition of c-Met might be a target for the development of chemotherapeutic agents for HCC, and especially those that are positive for expression of DCP.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carcinoma, Hepatocellular / drug therapy*
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Carcinoma, Hepatocellular / enzymology
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Carcinoma, Hepatocellular / pathology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Drug Screening Assays, Antitumor
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Humans
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Indoles / pharmacology
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Indoles / therapeutic use*
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Liver Neoplasms / drug therapy*
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Liver Neoplasms / enzymology
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Liver Neoplasms / pathology*
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Phosphorylation / drug effects
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Piperazines / pharmacology
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Piperazines / therapeutic use*
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use*
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Prothrombin / pharmacology
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Proto-Oncogene Proteins c-met / antagonists & inhibitors*
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Proto-Oncogene Proteins c-met / metabolism
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Sulfonamides / pharmacology
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Sulfonamides / therapeutic use*
Substances
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((3Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-((4-methylpiperazin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide)
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Indoles
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Piperazines
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Protein Kinase Inhibitors
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Sulfonamides
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Prothrombin
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Proto-Oncogene Proteins c-met
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Extracellular Signal-Regulated MAP Kinases