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

Chao-Chih Wu1, Chia-Sui Weng2, Yun-Ting Hsu1

  • 1Department of Medical Research, Mackay Memorial Hospital, New Taipei City, Taiwan.

Taiwanese Journal of Obstetrics & Gynecology
|January 15, 2019
PubMed
Abstract

Insights

The small molecule BMS-777607 effectively inhibits ovarian cancer cell growth by blocking c-MET signaling. This targeted therapy shows promise in preclinical models, warranting further investigation for ovarian cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Tyrosine-protein kinase MET (c-MET) is a prognostic marker and therapeutic target in ovarian cancer.
  • BMS-777607 is a small molecule inhibitor of MET and other protein kinases.

Purpose of the Study:

  • Investigate the mechanism of action of BMS-777607.
  • Evaluate the antitumor effect of BMS-777607 on ovarian cancer cells with activated c-MET.

Main Methods:

  • Identification of ovarian cancer cells with constitutively activated c-MET via Western blot.
  • Assessment of cell signaling, proliferation, apoptosis, migration, and ploidy after BMS-777607 treatment.
  • Evaluation of antitumor effects in a xenograft mouse model.

Main Results:

  • BMS-777607 significantly inhibited cell growth in ovarian cancer cells expressing c-MET.
  • Treatment reduced c-MET activation, inhibited downstream signaling, induced apoptosis and polyploidy, and decreased cell migration.
  • Tumor growth was inhibited in vivo in a mouse xenograft model.

Conclusions:

  • BMS-777607 demonstrates antitumor effects by blocking c-MET signaling and inhibiting Aurora B activity.
  • The findings support BMS-777607 as a potential therapeutic agent for ovarian cancer.
  • Combination treatments to enhance efficacy warrant future research.
Keywords:
Ovarian cancerTyrosine kinasec-MET

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