Huang, Y.; Fan, Y.; Zhao, Z.; Zhang, X.; Tucker, K.; Staley, A.; Suo, H.; Sun, W.; Shen, X.; Deng, B.; Pierce, S.R.; West, L.; Yin, Y.; Emanuele, M.J.; Zhou, C.; Bae-Jump, V. Inhibition of CDK1 by RO-3306 Exhibits Anti-Tumorigenic Effects in Ovarian Cancer Cells and a Transgenic Mouse Model of Ovarian Cancer. Int. J. Mol. Sci.2023, 24, 12375.
Huang, Y.; Fan, Y.; Zhao, Z.; Zhang, X.; Tucker, K.; Staley, A.; Suo, H.; Sun, W.; Shen, X.; Deng, B.; Pierce, S.R.; West, L.; Yin, Y.; Emanuele, M.J.; Zhou, C.; Bae-Jump, V. Inhibition of CDK1 by RO-3306 Exhibits Anti-Tumorigenic Effects in Ovarian Cancer Cells and a Transgenic Mouse Model of Ovarian Cancer. Int. J. Mol. Sci. 2023, 24, 12375.
Huang, Y.; Fan, Y.; Zhao, Z.; Zhang, X.; Tucker, K.; Staley, A.; Suo, H.; Sun, W.; Shen, X.; Deng, B.; Pierce, S.R.; West, L.; Yin, Y.; Emanuele, M.J.; Zhou, C.; Bae-Jump, V. Inhibition of CDK1 by RO-3306 Exhibits Anti-Tumorigenic Effects in Ovarian Cancer Cells and a Transgenic Mouse Model of Ovarian Cancer. Int. J. Mol. Sci.2023, 24, 12375.
Huang, Y.; Fan, Y.; Zhao, Z.; Zhang, X.; Tucker, K.; Staley, A.; Suo, H.; Sun, W.; Shen, X.; Deng, B.; Pierce, S.R.; West, L.; Yin, Y.; Emanuele, M.J.; Zhou, C.; Bae-Jump, V. Inhibition of CDK1 by RO-3306 Exhibits Anti-Tumorigenic Effects in Ovarian Cancer Cells and a Transgenic Mouse Model of Ovarian Cancer. Int. J. Mol. Sci. 2023, 24, 12375.
Abstract
Ovarian cancer is the deadliest gynecological malignancy of the reproductive organs in the United States. Cyclin-dependent kinase 1 (CDK1) is an important cell cycle regulatory protein that spe-cifically controls the G2/M phase transition of the cell cycle. RO-3306 is a selective, ATP-competitive, and cell-permeable CDK1 inhibitor that shows potent anti-tumor activity in multiple pre-clinical models. In this study, we investigated the effect of CDK1 expression on the prognosis of patients with ovarian cancer and the anti-tumorigenic effect of RO-3306 in both ovarian cancer cell lines and a genetically engineered mouse model of high-grade serous ovarian cancer (KpB model). In 147 patients with epithelial ovarian cancer, overexpression of CDK1 was significantly associated with poor prognosis, compared with a low expression group. RO-3306 significantly inhibited cellular proliferation, induced apoptosis, caused cellular stress, and reduced cell migration. Treatment of KpB mice with RO-3306 for four weeks showed a significant decrease in tumor weight under obese and lean conditions without obvious side effects. Overall, our results demonstrate that inhibition of CDK1 activity by RO-3306 effectively reduces cell proliferation and tumor growth, providing biological evidence for future clinical trials of CDK1 inhibitors in ovarian cancer
Medicine and Pharmacology, Obstetrics and Gynaecology
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