Abstract
Abstract Purpose: Ovarian cancer shows heterogeneous characteristics which cause chemoresistance and recurrence. The goal of this study was to elucidate characteristics common to various ovarian cancers in order to evaluate their potential for targeted therapy. Methods: Microarray results for cell lines of serous, mucinous, and brenner types of ovarian cancers were reanalyzed and validated via ovarian cancer cell lines, GEO datasets and TMA blocks. RO-3306 which is an inhibitor of Cdk1 and si-cdk1 was used to measure the growth rate of ovarian cancer cell lines via FACS analysis. In addition, combination treatment with RO-3306 and cisplatin was administered in vitro and in in vivo xenograft mouse model. Results: Microarray reanalysis revealed that expression of Cdk1 and cyclinB1 was higher in 5 types of ovarian cancer cell lines, 4 GEO datasets and ovarian cancer TMA blocks than in HOSE cells. Ovarian cancer TMA particularly showed increased level of cytoplasmic Cdk1 protein, but not in nucleus. When Cdk1 was inhibited by siRNA and a potent Cdk1 inhibitor (RO-3306), growth of ovarian cancer cells decreased, while G2/M arrest or apoptosis increased. In addition, tumor growth was significantly lesser in a xenograft mouse model treated with a combination of RO-3306 and cisplatin than in mice treated with each drug alone. Conclusions: Cdk1 is a promising gene for targeted anticancer therapy. It is expected that combined treatment with Cdk1 inhibitor and chemotherapeutic agents would maximize the effects of ovarian cancer treatment. Citation Format: Hanbyoul Cho, Wookyeom Yang, Ha-Yeon Shin, Eun-ju Lee, Doo-Byung Chay, Jae-Hoon Kim. Cyclin-dependent kinase 1 (Cdk1) is a promising therapeutic target to overcome ovarian cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C155.
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