TrxR靶向性的新型硒杂环化合物及其抗肿瘤分子机制

项目名称： TrxR靶向性的新型硒杂环化合物及其抗肿瘤分子机制

项目编号： No.21271002

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 陈填烽

作者单位： 暨南大学

项目金额： 78万元

中文摘要： 基于细胞通讯的化学药物设计已成为发现靶向性抗肿瘤药物的重要方式。硫氧还蛋白还原酶（TrxR）在多种肿瘤中高表达，通过多种途径促进其生长和恶化。目前认为TrxR是潜在的抗癌药物分子靶标，以TrxR为靶标发展新型抗肿瘤药物已成为国际上的研究热点。在前期工作中，我们发现硒杂环化合物能通过抑制TrxR活性而发挥抗肿瘤作用。在此基础上，本项目将深入研究硒杂环化合物与TrxR的相互作用机制，考察硒杂环化合物对 TrxR活性的影响，同时应用siRNA技术研究TrxR基因沉默对其下游凋亡信号通路的调节作用，阐述硒化合物对TrxR生物学功能的影响及其对 TrxR下游信号通路的调控作用，从而揭示TrxR在新型有机硒化合物诱导的肿瘤细胞凋亡分子机制中的作用，为寻找和开发出靶点清楚、机制明确的含硒新型抗肿瘤药物或先导药物提供理论和实验依据。

中文关键词： 硒杂环化合物；细胞凋亡；p53；信号转导；

英文摘要： Chemical drug design based on cancer cell signaling pathways has become an important strategy for discovery of targeting anticancer drugs. Thioredoxin reductase (TrxR) has been found overexpressed in many kinds of cancers, which play an important role in regulation of cell cycle progression and proliferation, and has attracted much attention as a novel anticancer drug target. Our previous studies have showed that synthetic selenadiazole derivatives exhibit their anticancer activities by inhibition of TrxR activities with the involvement of p53 signaling pathways. Based on these results, we would examine the interaction between the selenadiazole derivatives and TrxR. The effects of the synthetic compounds on intracellular TrxR activity and related signaling pathways will also be investigated in the present study. Moreover, siRNA technique will also be employed to examine the crosstalk between TrxR and other signaling pathways. It is anticipated that the results from this project may elucidate the role of TrxR in selenadiazole derivatives-induced cancer cell apoptosis, and help in searching for promising cancer-targeting chemotherapeutics with clear target and action mechanisms.

英文关键词： Selenadiazole derivatives；Cell apoptosis；p53；Signaling pathways；