噻唑烷类化合物抗肿瘤作用及其作用机制研究

项目名称： 噻唑烷类化合物抗肿瘤作用及其作用机制研究

项目编号： No.31271475

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 赵云峰

作者单位： 曲阜师范大学

项目金额： 68万元

中文摘要： 近年来，癌症严重威胁人类的身体健康。多药耐药性是造成肿瘤化疗失败的主要原因。本研究运用药理学、分子细胞生物学和化学遗传学的原理技术方法，对（MMPT、YFZ-11、YFZ-22、YFZ-38及YFZ-69）5种噻唑烷类化合物的抗肿瘤作用和可能的作用机制进行研究。首先通过体外抑瘤检测(SRB检测)与凋亡诱导检测，结合结构-活性分析把抑瘤效果好且能有效诱导肿瘤细胞凋亡（不依赖P-gp和p53表型）的化合物确认为先导化合物。再建立裸鼠移植肿瘤模型检测先导化合物的体内抗肿瘤活性。最后通过荧光实时定量PCR、生物信息学和RNA干扰等技术进一步探讨先导化合物的作用机制。项目期望筛选出对耐药细胞株有效而对正常细胞株低毒的噻唑烷类化合物，其抗肿瘤活性不依赖P-gp和p53表型，为抗肿瘤药物筛选提供一个新思路。

中文关键词： 噻唑烷类化合物；多药耐药性(MDR)；转录组测序；先导化合物；细胞凋亡

英文摘要： In recent years, cancer is the leading category of cancer threatening the health of people in many countries. The emergence of drug resistance is a major challenge to the success of cancer chemotherapy. Although the drug resistance can be caused by various mechanisms, the ultimate failure of chemotherapy often results from multidrug resistance (MDR), a phenotype of cross-resistance to multiple drugs with diverse chemical structures. The principle and technique of pharmacology, molecular cell biology and chemical genetics are used in this study. The overall objective of this proposal is to investigate the anti-cancer effects of new agents, thiazolidinone compounds (MMPT, YFZ-11, YFZ-22, YFZ-38 and YFZ-69), and the possible mechanism in inhibiting tumor cells growth. Firstly, the in vitro effects of thiazolidinone compounds (MMPT, YFZ-11, YFZ-22, YFZ-38 and YFZ-69), on cell viability and apoptosis of various cancer cells, including drug resistant cancer cells overexpressing P-glycoprotein, and wild-p53, mutant-p53 and null-p53 cancer cells, will be determined by sulforhodamine B (SRB) assay, H33258 stained assay, caspases activity assay, western blotting and so on. Together with these results, the antitumor activity and selectivity of thiazolidinone compounds (MMPT, YFZ-11, YFZ-22, YFZ-38 and YFZ-69) will be opti

英文关键词： Thiazolidinone Compounds；Multidrug Resistance；Transcriptome Sequencing；Lead Compound；Apoptosis