SIRT1基因诱导肿瘤细胞辐射耐受性的机理研究

项目名称： SIRT1基因诱导肿瘤细胞辐射耐受性的机理研究

项目编号： No.31300695

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 曹嘉

作者单位： 中国医学科学院

项目金额： 25万元

中文摘要： 在放疗过程中肿瘤往往产生辐射耐受，而产生辐射耐受的分子基础之一就是促凋亡蛋白Smac的低表达。Smac蛋白的表达和功能均依赖于NF-κB，而NF-κB的活性又受到SIRT1基因的调节。我们的前期研究也发现，SIRT1可抑制NF-κB，进而抑制辐射诱导的细胞炎症因子表达，提高细胞辐射后的存活率。因此，本项目将通过体外和体内实验研究SIRT1通过抑制NF-κB的活性，降低促凋亡蛋白Smac的表达，从而降低肿瘤细胞的辐射敏感性，明确SIRT1基因通过SIRT1-NF-κB-Smac通路诱导肿瘤细胞的辐射耐受性。本项目首次把SIRT1和Smac引入肿瘤辐射耐受的研究，从Smac蛋白表达的上游转录调控入手，探索SIRT1诱导辐射耐受的机理，为临床上具有辐射抗性肿瘤的放射治疗提供新的研究靶点，进而为临床上具有辐射抗性肿瘤的放射治疗提供新的研究思路和手段，在未来肿瘤放射增敏临床应用上具有重要意义和价值。

中文关键词： Smac；Sirt1；细胞凋亡；肿瘤；辐射敏感性

英文摘要： Tumor cells often present radiation-toleration in related to a radio-therapy. One of the molecular mechanisms of radiation-toleration is low expression of Smac, a protein that promotes apoptosis in tumor cells. The function and expression of Smac depend on NF-κB, and the activity of NF-κB is regulated by SIRT1. In our previous studies, we have discovered that SIRT1 inhibited the activity of NF-κB, and inhibited the expression of cellular inflammatory factors induced by radiation. Hence, survival rate of post-radiated tumor cells was increased. Therefor, we will study the radiosensitization of SIRT1 in tumor cells by in vitro and iv vivo experiments to identify that SIRT1 induced radiation toleration of tumor cells using SIRT1-NF-κB-Smac pathway. SIRT1 and Smac were studied in the tumor radio-toleration for the first time. Exploring the mechanisms of radiation toleration induced by SIRT1 begin with the upper transcriptional control of Smac protein. This study is expected to discover new markers, methods and thinks for radiation therapy of tumors with radiation resistance. Indeed, the execution of this study will show a great value in both of basis research and clinical application for tumor radiotherapy.

英文关键词： Smac；Sirt1；Apoptosis；Tumor；Radiosensitivity