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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

Chao-Chih Wu, Chia-Sui Weng, Yun-Ting Hsu, Chih-Long Chang

Taiwan J Obstet Gynecol. 2019 Jan;58(1):145-152.

PMID: 30638469

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1025720948	BMS-777607		1025720-94-8	Price

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