中枢神经系统特异性抑癌基因RRP22在胶质瘤中的促凋亡机制研究

项目名称： 中枢神经系统特异性抑癌基因RRP22在胶质瘤中的促凋亡机制研究

项目编号： No.81201990

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 陈若琨

作者单位： 郑州大学

项目金额： 23万元

中文摘要： 胶质瘤是中枢神经系统最常见的实体性肿瘤，治疗效果欠佳。RRP22为新发现的Ras超家族基因，唯一表达于神经系统的特性赋予了其作为基因诊断及靶向治疗胶质瘤的潜能。国外学者研究证明，RRP22表现出对细胞生长的负向调节特性,并推测其诱导了非依赖caspase系统的细胞凋亡。申请人在前期研究中发现RRP22过度表达可显著抑制胶质瘤细胞的生长增殖、侵袭迁移等特性，并通过激活线粒体通路诱导了细胞凋亡的发生。AIF通路作为线粒体激活后最重要的非依赖caspase通路已经得到了学者们的共识。那么，RRP22诱导的凋亡机制是否与AIF通路相关呢？本研究以胶质细胞系为模型，研究RRP22诱导细胞凋亡时AIF通路及caspase相关蛋白激活情况，从而进一步探讨RRP22诱导凋亡的相关机制。本课题将证实我们提出的"RRP22→AIF通路→凋亡"假说，为开发基于RRP22的胶质瘤分子靶向药物提供理论依据。

中文关键词： 胶质瘤；RRP22；AIF；HSDL2；细胞凋亡

英文摘要： Gliomas are one of the most frequently occurring primary tumors in the central nervous system. Although much progress has been made, the survival rate is still poor. Malignant gliomas, such as glioblastoma multiforme(GBM, WHO grade IV), are one of the most aggressive brain tumors with the poorest prognosis in spite of treatment with surgery, radiotherapy and conventional chemotherapy. With developments in molecular neurosurgery and recent advances in the understanding of genetic aberrations within gliomas, patient-targeted therapies have emerged to increase the therapeutic efficacy. However, most of the genetic aberrations found in gliomas were not specific, which is necessary for an accurate diagnosis. RRP22, a novel member of the Ras superfamily, is exclusively expressed in the central nervous system. According to our previous study, the results showed that the mRNA level in astrocytomas was significantly down-regulated compared to levels in normal tissues. As the pathological grade (WHO classification, 2007) increased, the expression decreased. Furthermore, the over-expression of RRP22 in U251 cells (a malignant glioma cell line) showed inhibited growth and decreased invasiveness and induced cell death. So far, the detailed mechanism of RRP22 on cell death is still unknow. According to the present report, Ca

英文关键词： glioma；RRP22；AIF；HSDL2；apoptosis