【摘 要】
：
Objective: Ovarian cancer is one of the most lethal of woman cancers, and its clinical therapeutic effect is unsatisfied currently.Dinaciclib, a novel small molecule multi-CDKs inhibitor of CDK1/2/5/9
【机 构】
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Department of Gynecology,the First Affiliated Hospital of Wenzhou Medical College,Wenzhou,Zhejiang 3
【出 处】
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2014医学科学前沿暨第三届个体化治疗与抗肿瘤药物研究新趋向研讨会
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Objective: Ovarian cancer is one of the most lethal of woman cancers, and its clinical therapeutic effect is unsatisfied currently.Dinaciclib, a novel small molecule multi-CDKs inhibitor of CDK1/2/5/9, is assessed in clinical trials for the treatment of several types of cancers.In this study, we determined the therapeutic efficacy of dinaciclib on human ovarian cancer cells.Methods: The cytotoxicity was measured by MTT assay.The combination index values were analyzed by CompuSyn software.The cell cycle distribution and cell apoptosis were detected using PI and Annexin V-FITC/PI staining by flow cytometric analysis.The expression levels of proteins were analyzed by western blot.Mouse xenograft model was established to observe the therapeutic effect in vivo.Results: The IC50 values of dinaciclib in multiple ovarian cancer cells were range from 0.01-0.02 μM.Treatment with dinaciclib induced cell cycle arrest and apoptosis,which were accompanied by marked decrease ofpRb and anti-apoptotic proteins such as Mcl-1, XIAP and survivin.Dinaciclib also caused ROS accumulation in the concentration-and time-dependent manner.The combination of dinaciclib and cisplatin was synergistic in ovarian cancer cells by induction of G2/M phase arrest and enhancement in apoptosis.In mouse xenograft experiment of ovarian cancer cells,tumor growth was moderately attenuated in either dinaciclib or cisplatin alone group,and more significantly in the combination group with the inhibition rates 57.7%,42.8% and 80.7%, respectively.Conclusion: Our data demonstrated that dinaciclib alone or used in combination with cispaltin is a promising experimental therapeutic strategy against ovarian cancer.
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