Cyclin-dependent kinase 11 (CDK11) is required for ovarian cancer cell growth in vitro and in vivo, and its inhibition causes apoptosis and sensitizes cells to paclitaxel

Abstract

Ovarian cancer is currently the most lethal gynecologic malignancy with limited treatment options. Improved targeted therapies are needed to combat ovarian cancer. Here, we report the identification of cyclin-dependent kinase 11 (CDK11) as a mediator of tumor cell growth and proliferation in ovarian cancer cells. Although CDK11 has not been implicated previously in this disease, we have found that its expression is upregulated in human ovarian cancer tissues and associated with malignant progression. Metastatic and recurrent tumors have significantly higher CDK11 expression when compared with the matched, original primary tumors. RNAimediated CDK11 silencing by synthetic siRNA or lentiviral shRNA decreased cell proliferation and induced apoptosis in ovarian cancer cells. Moreover, CDK11 knockdown enhances the cytotoxic effect of paclitaxel to inhibit cell growth in ovarian cancer cells. Systemic in vivo administration of CDK11 siRNA reduced the tumor growth in an ovarian cancer xenograft model. Our findings suggest that CDK11 may be a promising therapeutic target for the treatment of ovarian cancer patients.