Pembrolizumab promotes degradation of cyclin dependent kinase 6 and suppresses ovarian cancer progression in vitro

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.

CDK6; Cisplatin; Ovarian cancer; Pembrolizumab.