Cancerous inhibitor of protein phosphatase 2A regulates cisplatin resistance in ovarian cancer.
Cancerous inhibitor of protein phosphatase 2A regulates cisplatin resistance in ovarian cancer.
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DOI：
10.3892/ol.2018.9653
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发表时间：
2018-11
期刊：
影响因子：
2.9
通讯作者：
Wanbin Li;Hongyan Zhang;Linqing Yang;Yunfei Wang
中科院分区：
文献类型：
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作者：
Wanbin Li;Hongyan Zhang;Linqing Yang;Yunfei Wang
卵巢癌是最具侵袭性的妇科癌症。生存率低的原因是对铂类药物（包括顺铂）的化疗耐药性的发展。本研究旨在探讨蛋白磷酸酶2A （CIP2A）抑制剂诱导卵巢癌化疗耐药的机制。本研究初步研究了CIP2A在卵巢肿瘤组织、顺铂敏感的SKOV-3细胞株和顺铂耐药的卵巢癌SKOV-3CDDP/R细胞株中的表达。此外，在卵巢癌细胞中使用小干扰RNA敲除CIP2A，并分析这些细胞的化学敏感性。结果显示，CIP2A在卵巢癌患者和顺铂耐药卵巢癌SKOV-3CDDP/R细胞系中mRNA和蛋白水平均显著升高。敲除CIP2A后，细胞增殖能力下降，化学敏感性增强。CIP2A沉默显著促进顺铂诱导SKOV-3CDDP/R细胞的凋亡，提示CIP2A参与了卵巢癌细胞的顺铂耐药，CIP2A沉默增强了顺铂诱导的细胞凋亡。CIP2A可能被认为是调节卵巢癌顺铂治疗的潜在候选者。
Ovarian cancer is the most aggressive type of gynecological cancer. The cause of the poor survival rate is the development of chemotherapy resistance to platinum-based therapies, including cisplatin. The present study aimed to investigate the mechanism of cancerous inhibitor of protein phosphatase 2A (CIP2A)-induced chemoresistance in ovarian cancer. The present study initially investigated the expression of CIP2A in the ovarian tumor tissue, cisplatin-sensitive SKOV-3 cell line, and cisplatin-resistant ovarian carcinoma SKOV-3CDDP/R cell line. In addition, CIP2A was knocked down using small interference RNA in ovarian cancer cells and the chemosensitivity of these cells was analyzed. The results demonstrated that CIP2A expression was significantly higher in patients with ovarian cancer and in the cisplatin-resistant ovarian carcinoma SKOV-3CDDP/R cell line at the mRNA and protein levels. The proliferation and chemosensitivity were decreased and enhanced, respectively, when CIP2A was knocked down. CIP2A silencing significantly promoted the apoptosis induced by cisplatin in SKOV-3CDDP/R cells, suggesting that CIP2A participated in the cisplatin resistance of ovarian cancer cells and that CIP2A silencing enhanced the apoptosis induced by cisplatin. CIP2A may be considered as a potential candidate for modulating cisplatin therapy in ovarian cancer.