miR-497双重靶向抑制Akt/mTOR/P70s6k信号通路逆转卵巢癌顺铂耐药的机制研究

项目名称： miR-497双重靶向抑制Akt/mTOR/P70s6k信号通路逆转卵巢癌顺铂耐药的机制研究

项目编号： No.81502227

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 徐韶华

作者单位： 同济大学

项目金额： 16万元

中文摘要： 卵巢癌的顺铂耐药是卵巢肿瘤领域亟待解决的关键科学问题，研究表明Akt/mTOR/P70s6k信号通路与卵巢癌细胞顺铂耐药密切相关。项目组前期研究发现：miR-497在卵巢癌顺铂耐药患者和耐药细胞中低表达，同时伴mTOR/P70s6k高表达；mTOR/P70s6k是miR-497的靶基因；在卵巢癌细胞内上调miR-497的表达能诱导细胞凋亡。据此提出：miR-497通过双重靶向抑制Akt/mTOR/P70s6k信号通路，逆转卵巢癌细胞顺铂耐药性的假说。本项目拟采用卵巢癌顺铂耐药细胞株为研究对象，从细胞、动物和人组织样本水平阐明miR-497逆转卵巢癌顺铂耐药的作用机制，为卵巢癌顺铂耐药治疗提供新的策略和思路。

中文关键词： 卵巢肿瘤；非编码RNA；肿瘤耐药

英文摘要： Resistance to platinum-based chemotherapy presents a major obstacle to attempt to improve the prognosis of patients with ovarian cancer. Recently studies showed that Akt/mTOR/P70s6k pathway plays a central role in acquiring cisplatin-resistance of ovarian cancer. Our previously results has demonstrated that the expression level of miR-497 is downregulated, and meantime, the expression levels of mTOR/P70s6k are upregulated in cisplatin-resistant ovarian cancer cell compared with normal ovarian cancer cell. We also found that mTOR and P70s6k are potential targets of miR-497, and overexpression of miR-497 induced cell apoptosis in ovarian cancer cells. Based on these results, we proposed that overexpression of mir-497 sensitizes resistant ovarian cancer cell to cisplatin through down-regulation of mTOR and P70s6k expression. In this study, we aim to investigate the molecule mechanisms of miR-497 dual targeting Akt/mTOR/P70s6k signal pathway in cisplatin-resistant ovarian cancer cells, animal, and human tissue. The discovery of this study will benefit for development of new therapeutic treatment for cisplatin-resistant ovarian cancer.

英文关键词： ovarian cancer;noncoding RNA;drug resistance