Eiji Kunii1, Hiroaki Ozasa2, Tetsuya Oguri3, Ken Maeno1, Satoshi Fukuda1, Takehiro Uemura1, Osamu Takakuwa1, Hirotsugu Ohkubo1, Masaya Takemura1, Akio Niimi1. 1. Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, Japan. 2. Department of Multidisciplinary Cancer Treatment, Graduate School of Medicine Kyoto University, Sakyo-ku, Kyoto, Japan. 3. 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.
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. MATERIALS AND 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. CONCLUSION: 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. Copyright
BACKGROUND: The cellular N-methyl-N'-nitroso-guanidinehumanosteosarcoma 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. MATERIALS AND 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. CONCLUSION: 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. Copyright
Authors: Manja Friese-Hamim; Friedhelm Bladt; Giuseppe Locatelli; Uz Stammberger; Andree Blaukat Journal: Am J Cancer Res Date: 2017-04-01 Impact factor: 6.166