Cyclin-dependent kinase inhibitor dinaciclib potently synergizes with cisplatin in preclinical models of ovarian cancer
| Autor: | Xiu-Jie Zhu, Zhi Shi, Feng-Feng Xie, Zhang Wenji, Shi-Shi Pan, Qi-Wei Jiang, Xiu-Xiu Chen, Wu-Ming Qin, Jian-Ge Qiu, Li-Hua Gong, Feng Lin, You-Qiu Xue, Xiao-Jian Yan, Xiao-Long Mei |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cell cycle checkpoint
Blotting Western dinaciclib cisplatin Mice Nude Antineoplastic Agents Apoptosis Pyridinium Compounds Pharmacology combination therapy Cyclic N-Oxides chemistry.chemical_compound Inhibitory Concentration 50 Cyclin-dependent kinase Cell Line Tumor Survivin Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Dinaciclib Cell Proliferation Cisplatin Ovarian Neoplasms Cyclin-dependent kinase 1 Mice Inbred BALB C biology Indolizines Drug Synergism Cell Cycle Checkpoints medicine.disease Bridged Bicyclo Compounds Heterocyclic Xenograft Model Antitumor Assays Cyclin-Dependent Kinases XIAP Tumor Burden ovarian cancer HEK293 Cells Oncology chemistry biology.protein Female Ovarian cancer Reactive Oxygen Species medicine.drug Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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