甘氨双唑钠下调ATM信号通路对喉癌细胞放射增敏的机制研究

项目名称： 甘氨双唑钠下调ATM信号通路对喉癌细胞放射增敏的机制研究

项目编号： No.81201803

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1

项目作者： 曾越灿

作者单位： 中国医科大学

项目金额： 23万元

中文摘要： 喉癌是我国一种发病率和致死率较高的恶性肿瘤，放疗是治疗喉癌的重要手段，但放疗在喉癌的治疗中也存在一些局限：由于放射性组织损害而导致放疗剂量无法提高到足以杀灭绝大部分肿瘤细胞的程度；生长在肿瘤血管床较远隔的瘤细胞由于低氧状态而放射敏感性降低。因此，放射增敏剂在喉癌的放疗中就具有十分重要的地位和发展前景。甘氨双唑钠是我国自主开发的一种高效、低毒的放射增敏剂。本课题组前期的研究提示，甘氨双唑钠对喉癌有明显的放射增敏作用，然而，目前国内外关于甘氨双唑钠放射增敏的信号传导通路机制的研究尚无报道，迫切需要对其放射增敏的信号传导机制进行研究。本项目运用RT-PCR、Western Blotting、流式细胞术和RNAi等技术试图从信号传导通路方面，研究甘氨双唑钠是如何通过下调ATM信号传导通路来调节细胞周期检验点，从而实现放射增敏的。本课题将从崭新的角度-信号传导通路方面揭示甘氨双唑钠的放射增敏机制。

中文关键词： 放射敏感性；喉癌；ATM；甘氨双唑钠；信号通路

英文摘要： Laryngeal cancer is one of the high morbidity and mortality of malignant tumors in China. Radiotherapy is an important treatment of laryngeal cancer, but there are some limitations in this treatment: radiation doses can not be escalated enough to kill most of the tumor cells because of radiation-induced tissue damage; the tumor cells far away from vascular bed are less sensitive to radiation due to hypoxia. Therefore, the radiosensitizer has a very important position and a promising prospect for application in the radiotherapy of laryngeal cancer.Sodium glycididazole is an efficient radiosensitizer of low toxicities ,which was developed independently by scientists of China. Our previous studies suggest that sodium glycididazole has an significant radiosensitizing effect on laryngeal cancer. However,the radiosensitization mechanism of signal transduction pathways of sodium glycididazole is rarely reported currently both at home and abroad. It is of urgent need to investigate its radiosensitization mechanism of signal transduction pathways.The radiosensitization mechanism of how sodium glycididazole down-regulation ATM signal transduction pathway, which will affect the cell cycle checkpoint, will be investigated with lots of experimental techniques, such as RT-PCR, Western Blotting, flow cytometry ,RNAi,etc.This s

英文关键词： Radiosensitivity；laryngeal cancer；ATM；sodium glycididazole；signaling pathway