Nrf2-ARE信号通路与肿瘤发生及耐药性的关系

The Role of Nrf2-ARE Signal Pathway in Tumorigenesis and Drug Resistance

Nrf2-ARE信号转导通路是当前研究的热点,其核心分子包括核转录因子红细胞系-2p45(NF-E2)相关因子-2(nuclear factor erythroid-2p45-related factor2,Nrf2)、抗氧化反应元件(antioxidant response element,ARE)和Kelch样环氧氯丙烷相关蛋白-1(Kelch-like ECH-associated protein 1,Keap1)。Nrf2通过与ARE相互作用,诱导II相解毒酶、抗氧化酶及药物流出泵的表达,在癌症的化学预防中起重要作用。最新研究表明,Keap1和Nrf2的突变与肿瘤发生有关,也会导致肿瘤细胞对化疗药物产生耐药性。本文综述了有关Nrf2-ARE信号转导通路与肿瘤发生及耐药性的关系。

The important elements of Nrf2-ARE signal pathway are nuclear factor erythroid-2p45-related factor2 （Nrf2）, antioxidant response element （ARE） and Kelch-like ECH-associated proteinl （Keapl）. Nrf2 is a redox-sensitive transcription factor that regulates the expression of electrophile and xenobiotic detoxification enzymes and efflux pumps, which confer cytoprotection against oxidative stress and apoptosis in normal cells. However, treatment of cells with anticancer agent induces expression of Nrf2-regulated genes. Genetic alteration of Keapl and Nrf2 associated with tumorigenesis and confer resistance to chemotherapy. The development of the field regarding the role of Nrf2-ARE signal pathway in tumorigenesis and drug resistance is discussed.