2. Academic Validation
  3. Antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET

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

  • Taiwan J Obstet Gynecol. 2019 Jan;58(1):145-152. doi: 10.1016/j.tjog.2018.11.027.
Chao-Chih Wu 1,  Chia-Sui Weng 2,  Yun-Ting Hsu 1,  Chih-Long Chang 3
Affiliations

Affiliations

  • 1 Department of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan.
  • 2 Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan.
  • 3 Department of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan; Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medicine, Mackay Medical College, Sanchi, New Taipei City, Taiwan. Electronic address: [email protected].
PMID: 30638469 DOI: 10.1016/j.tjog.2018.11.027
Abstract

Objective: 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.

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 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.

Results: 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.

Conclusion: 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.

Keywords

Ovarian cancer; Tyrosine kinase; c-MET.

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