Early responses of the STAT3 pathway to platinum drugs are associated with cisplatin resistance in epithelial ovarian cancer

文献类型： 外文期刊

第一作者： Sheng, W. J.

作者： Sheng, W. J.;Jiang, H.;Zheng, J. H.;Wu, D. L.

作者机构：

关键词： Epithelial ovarian cancer;Cisplatin;Oxaliplatin;Nedaplatin;STAT3

期刊名称：BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH （ 影响因子：2.59； 五年影响因子：2.523 ）

ISSN： 0100-879X

年卷期： 2013 年 46 卷 8 期

页码：

收录情况： SCI

摘要： Cisplatin resistance remains one of the major obstacles when treating epithelial ovarian cancer. Because oxaliplatin and nedaplatin are effective against cisplatin-resistant ovarian cancer in clinical trials and signal transducer and activator of transcription 3 (STAT3) is associated with cisplatin resistance, we investigated whether overcoming cisplatin resistance by oxaliplatin and nedaplatin was associated with the STAT3 pathway in ovarian cancer. Alamar blue, clonogenic, and wound healing assays, and Western blot analysis were used to compare the effects of platinum drugs in SKOV-3 cells. At an equitoxic dose, oxaliplatin and nedaplatin exhibited similar inhibitory effects on colony-forming ability and greater inhibition on cell motility than cisplatin in ovarian cancer. Early in the time course of drug administration, cisplatin increased the expression of pSTAT3 (Tyr705), STAT3 alpha, VEGF, survivin, and Bcl-X-L, while oxaliplatin and nedaplatin exhibited the opposite effects, and upregulated pSTAT3 (Ser727) and STAT3 beta. The STAT3 pathway responded early to platinum drugs associated with cisplatin resistance in epithelial ovarian cancer and provided a rationale for new therapeutic strategies to reverse cisplatin resistance.

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