FGFR1对脑胶质瘤的调控机理及其可能作为药物靶点的研究

项目名称： FGFR1对脑胶质瘤的调控机理及其可能作为药物靶点的研究

项目编号： No.31501142

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 于涛

作者单位： 青岛大学

项目金额： 20万元

中文摘要： 脑胶质瘤发生率约占颅内肿瘤的46%，致死率极高，但近年来该肿瘤的总体疗效一直没有获得明显的改善。脑胶质瘤的病因、发病机制以及新治疗手段的探讨，是临床上亟待解决的难题。成纤维细胞生长因子受体（FGFRs）参与肿瘤细胞的增殖、凋亡和迁移，被认为是抗肿瘤的潜在重要靶点。目前在临床治疗中发现脑胶质瘤患者的脑组织内存在大量活性FGFR1的表达，但是其具体功能、与脑胶质瘤的关系以及调控机制尚不清楚。我们的前期研究发现FGFR1的活性抑制会明显降低胶质瘤细胞的增殖和分裂，且酪氨酸激酶Src可能作为主要蛋白参与调控。此外，我们还发现一类基于FGFR1为靶标的抑制剂PP2，它将作为工具小分子研究FGFR1与脑胶质瘤的关系。本课题将从细胞分子和整体动物水平深入探究FGFR1对脑胶质瘤发生发展的调控作用和分子机制。本项目的研究将丰富和完善脑胶质瘤的发病机理，为其预防及治疗开辟新的方向。

中文关键词： 成纤维细胞生长因子；脑胶质瘤；信号转导；激酶；转录因子

英文摘要： The incidence of cerebral gliomas account for about 46% of intracranial tumors, with high mortality rate. However, the overall curative effect of this disease has not been improved obviously in recent years. The etiology, pathogenesis and treatment methods of glioma is still the critical problem needed to be solved nowadays. Fibroblast growth factor receptor (FGFRs) has been proved to be involved in cell proliferation, apoptosis and migration, which is considered to be an important target against cancer. In our previous study, we found that inhibition of FGFR1 can lead to suppression of proliferation and division of C6 glioma cells, while Src kinase could be involved in this regulation. In addition, we also found novel inhibitor of PP2 targeted on FGFR1, which can effectively regulate the cell viability and proliferation of glioma cells. My group will apply modern immunology and cell biology technology to investigate the molecular mechanism of glioma regulated by FGFR1 from cell and whole animal aspects. This research can enrich the pathogenesis of glioma and open a new direction for its prevention and treatment.

英文关键词： fibroblast growth factor receptor;brain glioma;cell transduction;kinase;transcription factor