上皮性卵巢癌铂类药物继发性耐药机制复杂，目前仍是基础和临床研究难题。我们利用基因芯片技术分析发现内质网核苷酸水解酶Entpd5在铂类药物耐药的卵巢癌细胞中表达显著升高，且Entpd5在铂类药物治疗后复发的卵巢癌组织中的表达也显著增高；增加Entpd5的表达，可以抑制铂类药物对细胞的杀伤能力，而敲除Entpd5基因，可提高卵巢癌细胞对铂类药物的敏感性，细胞的耐药性被逆转。由此我们推测，Entpd5参与卵巢癌对铂类药物耐药性的调节。本研究拟采用蛋白质组学技术、基因敲除、基因转染和western blot等分子、细胞生物学和遗传学方法，在细胞和动物水平，分析Entpd5与卵巢癌的铂类药物耐药性的关系，并用临床标本加以验证，探讨Entpd5参与上皮性卵巢癌对铂类药物继发耐药的调节机制，深入阐明其分子机理以及信号调节途径，为寻找有效逆转耐药的新靶点和个体化治疗提供新思路。

The mechanisms of acquired cisplatin-resistance are complicated and remain as the key problems in basic and clinical research of ovarian epithelial cancer. Using an expression profiling analysis of microarray, we found that the Entpd5, an ectonucleoside triphosphate diphosphohydrolase 5 in the endoplasmic-reticulum (ER), was significantly upregulated in both cisplatin-resistant cells and clinical recurrent ovarian cancer samples. Overexpression of Entpd5 protected ovarian cancer cells apoptosis caused by cisplatin, whereas knockdown of Entpd5 enhanced cisplatin induced cell apoptosis, implicating Entpd5 may play a role of regulation of drug resistance in ovarian cancer. We hypothesize that Entpd5 plays the important role in regulation of ovarian cancers resistance against cell death by chemotherapy treatment. To test this hypothesis, we plan to use the functional and quantitative proteomic technology- stable isotope labeling by amino acids in cell culture (SILAC), gene transfection, gene knockout and other molecular and cell biology and genetics methods to: 1) determine the relationship between Entpd5 expression and cisplatin-resistance in ovarian epithelial cancer; 2) validating the role of Entpd5 in role of regulation of drug resistance in ovarian epithelial cancers; 3) elaborating mechanisms underlying this Entpd5 mediated regulation of recurrence and cisplatin-resistance of ovarian cancer. Our studies will provide mechanistic insight toward regulation of drug resistance and recurrence in ovarian cancers by Entpd5 and its signaling pathway. The knowledge from our studies will also provide a new therapeutic target and strategy of drug resistance reverse and personalized precise treatment for patients with cisplatin-resistant ovarian cancer.