稳态反应氧族介导肿瘤多药耐药的量效关系及机制研究

项目名称： 稳态反应氧族介导肿瘤多药耐药的量效关系及机制研究

项目编号： No.U1204830

项目类型： 联合基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 岑娟

作者单位： 河南大学

项目金额： 30万元

中文摘要： 本项目关注肿瘤多药耐药细胞和敏感细胞的差异，发现反应氧族（ROS）可能是耐药形成和维持的重要机制。首先选用成对的细胞株与临床样本作为研究对象，验证ROS含量差异的共性；然后以长期培养方式建立有不同稳态强度的ROS的成对细胞模型，辅以高内涵活细胞成像系统进行动态监控，从而揭示ROS含量与多药耐药之间较为精准的量效关系，为逆转多药耐药提供ROS的调控范围；之后利用western blot法、Elisa法和高内涵活细胞成像法等实验手段，有针对地筛选出ROS敏感的、具有多药耐药特异性的信号转导分子，在此基础上，通过抑制剂、基因沉默技术的靶向定位，理清ROS调控谷胱甘肽合成和P-糖蛋白功能、表达的信号转导过程，阐明ROS介导多药耐药的机制。研究结果有助于进一步揭示多药耐药的机理，并为耐药肿瘤的药物治疗寻找新的靶点、为形成更安全有效的治疗策略提供实验参考和理论依据。

中文关键词： 反应氧族；多药耐药；MCF-7 细胞；信号通路；

英文摘要： This project focuses on the difference between multidrug resistant cell and sensitive cell to find that the formation and maintenance mechanism of multidrug resistance may due to the reactive oxygen species (ROS). Firstly, the multidrug resistant cell lines and clinical samples with their parent sensitive ones are utilised to validate the common difference of ROS level. Secondly, pairs of cell models which have different levels of steady ROS will be built by long term incubation with oxidant or antioxidant. The high content living cell imaging system (HCS) could be used as a real-time monitor. Therefore, the specific dose-effect relationship between ROS content and multidrug resistance will be discovered, for providing the regulation direction of ROS content to reverse multidrug resistance. Thirdly, western blot, Elisa and the HCS will be applied to screen the multidrug resistant specific signal transduction molecules which are sensitive to ROS. Then, the inhibitors and siRNA technicals will help to clarify how ROS regulates the function and expression of P-gp as well as the and the synthesis of GSH. It will elucidates the mechanism of ROS mediated multidrug resistance. These findings will further reveal the mechanism of multidrug resistance, and facilitate to find new targets for multidrug resistant reversal, t

英文关键词： Reactive oxygen species；multidrug resistance；MCF-7 cells；signal pathways；