Targeting nrf2 signaling to combat chemoresistance.
Targeting nrf2 signaling to combat chemoresistance.
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DOI：
10.15430/jcp.2014.19.2.111
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发表时间：
2014-06
影响因子：
2.5
通讯作者：
Song YS
中科院分区：
文献类型：
--
作者：
No JH;Kim YB;Song YS
核因子E2相关因子2(NRF2)是一种转录因子，可上调一系列基因的表达，以对抗氧化和亲电应激。Kelch样ECH相关蛋白1(Keap1)被活性氧修饰，通过逃避降解来稳定Nrf2。然后，NRF2与各种基因启动子区域上的抗氧化反应元件(ARE)结合。Keap1-Nrf2-ARE通路的激活在多种植物化学物质的化学预防作用中起着关键作用。然而，Nrf2可以保护癌细胞免受氧化应激的影响，并促进细胞增殖。此外，最近的研究表明，Nrf2通路的激活是化疗药物耐药的关键。本综述的目的是为使用Nrf2抑制剂克服化疗耐药提供分子基础。
Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that upregulates expression of a battery of genes to combat oxidative and electrophilic stress. Modification of Kelch-like ECH-associated protein 1 (Keap1) by reactive oxygen species stabilizes Nrf2 by escaping from degradation. Nrf2 then binds to antioxidant response elements (AREs) on the promoter region of various genes. Activation of the Keap1-Nrf2-ARE pathway plays critical roles in the chemopreventive effect of various phytochemicals. However, Nrf2 can protect cancer cells from oxidative stress and promote cell proliferation. Moreover, recent studies reveal that activation of the Nrf2 pathway is critical for resistance to chemotherapeutic agents. The aim of this review is to provide a molecular basis for the use of Nrf2 inhibitors in overcoming chemoresistance.