Pembrolizumab promotes degradation of cyclin dependent kinase 6 and suppresses ovarian cancer progression in vitro
Abstract Pembrolizumab is a novel humanized anti-PD-1 monoclonal antibody capable of enhancing T-cell mediated antitumor immunity. However, the function of pembrolizumab on tumor cells themselves and relative molecular mechanism in ovarian cancer remain unknown. Our study demonstrated pembrolizumab...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-11043-5 |
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| author | Yi Wu Ziyan Xu Zuqiang Kou Qiuling Ye Liting Chen Boyu Gou |
| author_facet | Yi Wu Ziyan Xu Zuqiang Kou Qiuling Ye Liting Chen Boyu Gou |
| author_sort | Yi Wu |
| collection | DOAJ |
| description | Abstract Pembrolizumab is a novel humanized anti-PD-1 monoclonal antibody capable of enhancing T-cell mediated antitumor immunity. However, the function of pembrolizumab on tumor cells themselves and relative molecular mechanism in ovarian cancer remain unknown. Our study demonstrated pembrolizumab exerted remarkable suppressive impacts on proliferation, colony formation and migration of ovarian cancer cells in vitro. Furthermore, pembrolizumab treatment delayed cell cycle progress from G1 to S phase transition and suppressed cell growth in ovarian cancer cells. Mechanistically, pembrolizumab decreased the stability of CDK6 protein through a polyubiquitin-mediated proteasomal degradation pathway. Meanwhile, pembrolizumab treatment dose-dependently reduced Snail, Vimentin and N-cadherin expressions and enhanced E-cadherin expressions. Additionally, the combined treatment of pembrolizumab and cisplatin effectively enhanced anti-proliferative effect of cisplatin on HO-8910 cells. These findings suggested pembrolizumab efficiently suppressed malignant progression of ovarian cancer cells and facilitated proteasomal degradation of CDK6 and increased cisplatin inhibition of HO-8910 cells proliferation, therefore providing a promising therapeutic strategy for ovarian cancer. |
| format | Article |
| id | doaj-art-8d3c387c65734a4dac54fa0c04b8f6e7 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-8d3c387c65734a4dac54fa0c04b8f6e72025-08-20T04:02:51ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-11043-5Pembrolizumab promotes degradation of cyclin dependent kinase 6 and suppresses ovarian cancer progression in vitroYi Wu0Ziyan Xu1Zuqiang Kou2Qiuling Ye3Liting Chen4Boyu Gou5Department of Pathogenic Biology, Shenyang Medical CollegeMajor in Anesthesiology, Shenyang Medical CollegeDepartment of Logistics, Shenyang Ligong UniversityMajor in Medical Laboratory Technology, School of Basic Medicine, Shenyang Medical CollegeMajor in Medical Laboratory Technology, School of Basic Medicine, Shenyang Medical CollegeMajor in Medical Laboratory Technology, School of Basic Medicine, Shenyang Medical CollegeAbstract Pembrolizumab is a novel humanized anti-PD-1 monoclonal antibody capable of enhancing T-cell mediated antitumor immunity. However, the function of pembrolizumab on tumor cells themselves and relative molecular mechanism in ovarian cancer remain unknown. Our study demonstrated pembrolizumab exerted remarkable suppressive impacts on proliferation, colony formation and migration of ovarian cancer cells in vitro. Furthermore, pembrolizumab treatment delayed cell cycle progress from G1 to S phase transition and suppressed cell growth in ovarian cancer cells. Mechanistically, pembrolizumab decreased the stability of CDK6 protein through a polyubiquitin-mediated proteasomal degradation pathway. Meanwhile, pembrolizumab treatment dose-dependently reduced Snail, Vimentin and N-cadherin expressions and enhanced E-cadherin expressions. Additionally, the combined treatment of pembrolizumab and cisplatin effectively enhanced anti-proliferative effect of cisplatin on HO-8910 cells. These findings suggested pembrolizumab efficiently suppressed malignant progression of ovarian cancer cells and facilitated proteasomal degradation of CDK6 and increased cisplatin inhibition of HO-8910 cells proliferation, therefore providing a promising therapeutic strategy for ovarian cancer.https://doi.org/10.1038/s41598-025-11043-5PembrolizumabOvarian cancerCDK6Cisplatin |
| spellingShingle | Yi Wu Ziyan Xu Zuqiang Kou Qiuling Ye Liting Chen Boyu Gou Pembrolizumab promotes degradation of cyclin dependent kinase 6 and suppresses ovarian cancer progression in vitro Scientific Reports Pembrolizumab Ovarian cancer CDK6 Cisplatin |
| title | Pembrolizumab promotes degradation of cyclin dependent kinase 6 and suppresses ovarian cancer progression in vitro |
| title_full | Pembrolizumab promotes degradation of cyclin dependent kinase 6 and suppresses ovarian cancer progression in vitro |
| title_fullStr | Pembrolizumab promotes degradation of cyclin dependent kinase 6 and suppresses ovarian cancer progression in vitro |
| title_full_unstemmed | Pembrolizumab promotes degradation of cyclin dependent kinase 6 and suppresses ovarian cancer progression in vitro |
| title_short | Pembrolizumab promotes degradation of cyclin dependent kinase 6 and suppresses ovarian cancer progression in vitro |
| title_sort | pembrolizumab promotes degradation of cyclin dependent kinase 6 and suppresses ovarian cancer progression in vitro |
| topic | Pembrolizumab Ovarian cancer CDK6 Cisplatin |
| url | https://doi.org/10.1038/s41598-025-11043-5 |
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