title: Reversal of c-MET-mediated Resistance to Cytotoxic Anticancer Drugs by a Novel c-MET Inhibitor TAS-115.
abstract: BACKGROUND
  The cellular N-methyl-N'-nitroso-guanidine human osteosarcoma transforming gene (c-MET) protein is the receptor tyrosine kinase for hepatocyte growth factor. We recently found that c-MET protein expression and activation were enhanced in the majority of small cell lung cancer cell lines with cytotoxic anticancer drug resistance, and that down-regulation of c-MET reduced resistance to these drugs.
  
  
  METHODS
  Expression of c-MET was studied in three non-small cell lung cancer (NSCLC) cell lines, including six resistant cell strains to cytotoxic anticancer drugs. To assess the effect of c-MET activation on drug resistance, we studied drug sensitivity in the presence of a novel c-MET inhibitor TAS-115.
  
  
  RESULTS
  c-MET expression and activation are also enhanced in some cytotoxic anticancer drug-resistant NSCLC cell lines, and inhibition of c-MET activation by TAS-115 reduced resistance of these cell lines to anticancer drugs.
  
  
  CONCLUSIONS
  The mechanism of cellular resistance to anticancer drugs via hepatocyte growth factor/c-MET signal activation is not restricted to small cell lung cancer cell lines, and TAS-115 might be able to reverse the drug resistance of these cancer cells.
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kunii
authors.affiliation: Department of Multidisciplinary Cancer Treatment, Graduate School of Medicine Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ozasa
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan t-oguri@med.nagoya-cu.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oguri
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Maeno
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuda
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Uemura
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takakuwa
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ohkubo
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Takemura
authors.affiliation: Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Niimi
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology*; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C066855:HGF protein, human; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D013890:Thiourea; C000590217:4-(2-fluoro-4-((((2-phenylacetyl)amino)thioxomethyl)amino)phenoxy)-7-methoxy-N-methyl-6-quinolinecarboxamide
keywords: Lung cancer; TAS-115; anticancer drug combinations; c-MET inhibitor; drug resistance