Antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-01-01
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| Series: | Taiwanese Journal of Obstetrics & Gynecology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1028455918303012 |
| _version_ | 1819295856131571712 |
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| author | Chao-Chih Wu Chia-Sui Weng Yun-Ting Hsu Chih-Long Chang |
| author_facet | Chao-Chih Wu Chia-Sui Weng Yun-Ting Hsu Chih-Long Chang |
| author_sort | Chao-Chih Wu |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-24T04:48:51Z |
| format | Article |
| id | doaj.art-7aea901a60cd40c187f86863c8e47e62 |
| institution | Directory Open Access Journal |
| issn | 1028-4559 |
| language | English |
| last_indexed | 2024-12-24T04:48:51Z |
| publishDate | 2019-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Taiwanese Journal of Obstetrics & Gynecology |
| spelling | doaj.art-7aea901a60cd40c187f86863c8e47e622022-12-21T17:14:37ZengElsevierTaiwanese Journal of Obstetrics & Gynecology1028-45592019-01-01581145152Antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-METChao-Chih Wu0Chia-Sui Weng1Yun-Ting Hsu2Chih-Long Chang3Department of Medical Research, Mackay Memorial Hospital, New Taipei City, TaiwanDepartment of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, TaiwanDepartment of Medical Research, Mackay Memorial Hospital, New Taipei City, TaiwanDepartment 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; Corresponding author. Department of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Section 2, Chung-Shan North Road, Taipei, Taiwan. Fax: +886 2 25232448.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-METhttp://www.sciencedirect.com/science/article/pii/S1028455918303012 |
| spellingShingle | Chao-Chih Wu Chia-Sui Weng Yun-Ting Hsu Chih-Long Chang Antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET Taiwanese Journal of Obstetrics & Gynecology |
| title | Antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET |
| title_full | Antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET |
| title_fullStr | Antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET |
| title_full_unstemmed | Antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET |
| title_short | Antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET |
| title_sort | antitumor effects of bms 777607 on ovarian cancer cells with constitutively activated c met |
| url | http://www.sciencedirect.com/science/article/pii/S1028455918303012 |
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