胶质瘤中IDH1突变的肿瘤生长抑制与放化疗增敏作用及其机制

项目名称： 胶质瘤中IDH1突变的肿瘤生长抑制与放化疗增敏作用及其机制

项目编号： No.81201975

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： 施金龙

作者单位： 南通大学

项目金额： 23万元

中文摘要： 异柠檬酸脱氢酶1(IDH1)基因突变在脑胶质瘤中发生频繁，具有胶质瘤特异性，与患者预后改善密切相关，但其保护机制和对肿瘤治疗的意义尚不明确。前期研究发现：胶质瘤细胞中过表达突变型IDH1后，胞内活性氧(ROS)水平升高，肿瘤细胞生长明显抑制。我们推测，IDH1突变体诱导ROS水平升高是抑制肿瘤生长的重要机制，且可能具有放化疗增敏作用。本项目在前期研究基础上，利用基因过表达、siRNA干扰、蛋白质芯片、荷瘤动物模型等技术进一步验证IDH1突变的肿瘤生长抑制作用，探讨ROS介导的可能信号通路；通过体外、体内实验明确IDH1突变的胶质瘤放化疗增敏作用并筛选化疗敏感药物。通过本项目的研究，阐明IDH1突变改善预后的具体机制，为IDH1突变对胶质瘤治疗效果的预测和个体化治疗方案的选择提供实验基础，并为胶质瘤靶向性治疗提供新的靶标。

中文关键词： 异柠檬酸脱氢酶1；胶质瘤；活性氧；生长抑制；化疗

英文摘要： Isocitrate dehydrogenase 1 gene (IDH1) mutation which is characterized by glioma occurs frequently and closely relates to a better outcome. However, the protective mechanism and value of treatment in glioma still remain indefinite. Our previous studies found that the level of intracellular reactive oxygen species (ROS) elevated while the growth of glioma cells, which overpressed mutated IDH1 gene , was significantly inhibited. We speculate that the rise in ROS level induced by IDH1 mutation is an important mechanism of tumor growth inhibition, and may have sensitisation effect to radiotherapy and chemotherapy. On the basis of previous studies, the project will use the technologies of gene overexpression, siRNA interference, protein chip and tumor-bearing animal models to further verify the glioma growth inhibition effect of IDH1 mutation, to investigate the potential ROS-mediated signaling pathway, to make clear the radiotherapy and chemotherapy sensitisation effect stimulated by IDH1 mutation and screen sensitive chemotherapy drugs through in vitro and in vivo experiments. The purpose of the project is to elucidate the specific mechanisms of the improvement in prognosis of IDH1 mutation, to provide the experimental basis for predicting the therapeutic effect and selecting individualized treatment scheme of IDH1

英文关键词： IDH1；Glioma；ROS；Growth inhibition；Chemotherapy