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Taiwanese Journal of Obstetrics & Gynecology
Antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET r> a Department of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan
b Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan
c Department of Medicine, Mackay Medical College, Sanchi, New Taipei City, Taiwan
Objective: Tyrosine-protein kinase MET (c-MET) has been reported to be a prognostic marker and suit-able therapeutic target for ovarian cancer. BMS-777607, a small molecule, can inhibit MET and other protein kinase activities. The present study was conducted to investigate the mechanism of action and antitumor effect of BMS-777607 on ovarian cancer cells with constitutively activated c-MET.
Materials and methods: Ovarian cancer cells with constitutively activated c-MET were first identified through Western blot analysis. Bio-behaviors, including signal transduction, proliferation, apoptosis, and migration, of the cells with constitutively activated c-MET were evaluated after BMS-777607 treatment. Liu's stain and immunological staining of a-tubuline were performed to evaluate the ploidy of the cells. A xenograft mouse model was also used to evaluate the antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET.
Results: BMS-777607 could induce the highest inhibition of cell growth in ovarian cancer cells consti-tutively expressing c-MET. Treating SKOV3 cells with BMS-777607 could reduce c-MET activation and inhibit downstream cell signaling, thus causing cell apoptosis and polyploidy as well as cell cycle and cell migration inhibition. This molecule also inhibited tumor growth in a mouse xenograft model of SKOV3 ovarian cancer cells in vivo.