Antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET

• Published in: Taiwanese journal of obstetrics & gynecology 2019-01, Vol.58 (1), p.145-152
• Main Authors: Wu, Chao-Chih, Weng, Chia-Sui, Hsu, Yun-Ting, Chang, Chih-Long
• Format: Article
• Language: English
• Subjects: c-MET; Ovarian cancer; Tyrosine kinase
• ISSN: 1028-4559
• DOI: 10.1016/j.tjog.2018.11.027

Tyrosine-protein kinase MET (c-MET) has been reported to be a prognostic marker and suitable 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. 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 α-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. BMS-777607 could induce the highest inhibition of cell growth in ovarian cancer cells constitutively 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. BMS-777607 exhibits antitumor effects on ovarian cancer cells that constitutively express c-MET through c-MET signaling blockade and the inhibition of Aurora B activity. Combination treatments to enhance the effects of BMS-777607 warrant investigation in the future.