Nrf2在肿瘤耐药中的作用及其机制研究

项目名称： Nrf2在肿瘤耐药中的作用及其机制研究

项目编号： No.30801410

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 胡容

作者单位： 中国药科大学

项目金额： 19万元

中文摘要： Nrf2 (nuclear factor E2 -related factor 2) 是细胞调节抗氧化应激反应的重要转录因子，传统观点认为Nrf2-ARE通路的激活是一种保护细胞、预防肿瘤的手段。最新研究提示，Nrf2与肿瘤细胞对化疗药物的耐受性相关。本课题研究结果表明，Nrf2不仅可在正常组织中诱导下游的II相代谢酶和抗氧化酶而起到细胞保护作用，也在肿瘤细胞中激活下游的HO-1和NQO-1等基因，抵抗凋亡进而引发肿瘤细胞耐药性。诱导Nrf2水平可引发肿瘤细胞耐药，而抑制其水平可逆转耐药。同时发现中药单体汉黄芩素可通过抑制Nrf2通路逆转耐药。本课题阐明了Nrf2在乳腺癌耐药中的作用及相关机制，为逆转肿瘤耐药性的研究提供了新的方向。

中文关键词： Nrf2；肿瘤耐药性；细胞凋亡；汉黄芩素

英文摘要： Nrf2 (nuclear factor E2 -related factor 2) is an important transcription factor which regulates the anti-oxidant response in the cell. Activation of the nrf2-ARE pathway has been known to protect the cells and therefore, has chemopreventive functions. Recently, it has been discovered that this pathway may play a role in tumor resistance. Our results showed that nrf2 can not only induce the phase II drug metabolizing enzymes and anti-oxidant enzymes to exert its cytoprotective function in normal cells, but also induce the downstream HO-1 and NQO-1 genes in MCF-7 cells, indicating that Nrf2 may be able to protect tumor cells through up-regulating cytoprotective genes, resistance to apoptosis, and therefore leading to tumor resistance. We also found that wogonin down-regulated the Nrf2-mediated signaling and reverses drug resistance in MCF-7/ADM cells. This study demonstrated how nrf2 regulates its downstream pathways in tumor cells, the role of nrf2 in tumor resistance and the underlying mechanisms, and it may provide a new direction to study tumor resistance.

英文关键词： Nrf2; tumor resistance; apoptosis; wogonin