Aurora-A通过抑制细胞衰老介导卵巢癌化疗抵抗的机制研究

项目名称： Aurora-A通过抑制细胞衰老介导卵巢癌化疗抵抗的机制研究

项目编号： No.81502228

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： 孙会贞

作者单位： 复旦大学

项目金额： 18万元

中文摘要： Aurora-A激酶与细胞衰老均可调节细胞有丝分裂和周期，并对肿瘤发生、发展、治疗等具有重要影响。申请人在文献报道以及前期研究基础上，发现Aurora-A在约半数卵巢癌组织中高表达，且可抑制p53/p21，p16/Rb，BRCA1/2等促衰老蛋白表达。细胞衰老增加肿瘤化疗敏感性，此与Aurora-A介导多种肿瘤化疗抵抗的作用相反。我们推断Aurora-A与细胞衰老以及卵巢癌化疗敏感性之间存在重要关联。预实验结果表明，Aurora-A明显降低卵巢癌细胞衰老水平以及紫杉醇化疗敏感性，并影响衰老相关蛋白表达。最终本申请者提出假说 “Aurora-A可通过抑制细胞衰老介导卵巢癌化疗抵抗”。本项目拟在卵巢癌中从分子、细胞、动物和组织临床水平上，探讨Aurora-A与细胞衰老，化疗敏感性之间的关系以及其机理，并寻求新的药物靶向分子，为Aurora-A高表达卵巢癌的全面治疗找到新的方法。

中文关键词： C24_卵巢肿瘤；Aurora-A；细胞衰老；化疗敏感性

英文摘要： Both of Aurora-A kinase and cell senescence regulate cell division and cell cycle, which plays great roles in cancer, included in origin, development and therapy. As is shown in literatures and our previous studies, Aurora-A is highly expressed in about half of neoplastic ovarian tissue samples, and inhibits the expression of senescence promoting proteins such as p53/p21, p16/Rb, and BRCA1/2. Cell senescence promotes tumor chemo-sensitivity, which is opposed to Aurora-A-induced tumor chemo-resistance. We infer an important association among Aurora-A, cell senescence and ovarian cancer chemo-sensitivity. Then, as expected, we found that Aurora-A decreased ovarian cancer cell senescence and chemo-sensitivity of paclitaxel obviously accompanied by changed senescence-associated proteins in our pre-experiment. Therefore, we hypothesize that Aurora-A induces ovarian cancer chemo-resistance by inhibition cell senescence. The program is planned to investigate the association among Aurora-A , cell senescence and chemo-resistance, and to explore the mechanisms via the study of molecules, cells, animals and tissues so as to find new targeted molecules for the comprehensive therapy of Aurora-A high expressed ovarian cancers.

英文关键词： ovarian cancer;Aurora-A;cell senescence;chemo-sensitivity