AI Article Synopsis

  • Ovarian cancer is a highly lethal disease in women, and current treatments are not very effective, prompting research into new therapeutic options.
  • Dinaciclib, a novel small molecule that inhibits specific cyclin-dependent kinases (CDKs), has shown promising effects on inhibiting cell growth, inducing cell cycle arrest, and promoting apoptosis in ovarian cancer cells, primarily through increased reactive oxygen species (ROS).
  • Combining dinaciclib with cisplatin enhances the anticancer effects, leading to improved cell cycle arrest and reduced tumor growth in preclinical models, suggesting that this combination therapy could be a promising approach for treating ovarian cancer.

Article Abstract

Ovarian cancer is one of the most lethal of woman cancers, and its clinical therapeutic outcome currently is unsatisfied. Dinaciclib, a novel small molecule inhibitor of CDK1, CDK2, CDK5 and CDK9, is assessed in clinical trials for the treatment of several types of cancers. In this study, we investigated the anticancer effects and mechanisms of dinaciclib alone or combined with cisplatin in ovarian cancer. Dinaciclib alone actively induced cell growth inhibition, cell cycle arrest and apoptosis with the increased intracellular ROS levels, which were accompanied by obvious alterations of related proteins such as CDKs, Cyclins, Mcl-1, XIAP and survivin. Pretreatment with N-acety-L-cysteine significantly blocked ROS generation but only partially rescued apoptosis triggered by dinaciclib. Moreover, the combination of dinaciclib with cisplatin synergistically promoted cell cycle arrest and apoptosis, and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. Altogether, dinaciclib potently synergizes with cisplatin in preclinical models of ovarian cancer, indicating this beneficial combinational therapy may be a promising strategy for treatment of ovarian cancer.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4558126PMC
http://dx.doi.org/10.18632/oncotarget.3717DOI Listing

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