Tian Yu, Tang Lixin, Wang Xin, Ji Yanqin, Tu Yanyang
Research Center, Huizhou Central People's Hospital, Guangdong Medical University Huizhou, Guangdong, China.
School of Public Health, Benedictine University Lisle, Illinois, USA.
Am J Cancer Res. 2024 Aug 25;14(8):3935-3961. doi: 10.62347/LZVO6743. eCollection 2024.
The nuclear factor-erythroid 2-related factor 2 (Nrf2) is able to control the redox balance in the cells responding to oxidative damage and other stress signals. The Nrf2 upregulation can elevate the levels of antioxidant enzymes to support against damage and death. In spite of protective function of Nrf2 in the physiological conditions, the stimulation of Nrf2 in the cancer has been in favour of tumorigenesis. Since the dysregulation of molecular pathways and mutations/deletions are common in tumors, Nrf2 can be a promising therapeutic target. The Nrf2 overexpression can prevent cell death in tumor and by increasing the survival rate of cancer cells, ensures the carcinogenesis. Moreover, the induction of Nrf2 can promote the invasion and metastasis of tumor cells. The Nrf2 upregulation stimulates EMT to increase cancer metastasis. Furthermore, regarding the protective function of Nrf2, its stimulation triggers chemoresistance. The natural products can regulate Nrf2 in the cancer therapy and reverse drug resistance. Moreover, nanostructures can specifically target Nrf2 signaling in cancer therapy. The current review discusses the potential function of Nrf2 in the proliferation, metastasis and drug resistance. Then, the capacity of natural products and nanostructures for suppressing Nrf2-mediated cancer progression is discussed.
核因子红细胞 2 相关因子 2（Nrf2）能够在细胞中响应氧化损伤和其他应激信号时控制氧化还原平衡。Nrf2 的上调可提高抗氧化酶水平，以抵御损伤和细胞死亡。尽管 Nrf2 在生理条件下具有保护作用，但在癌症中刺激 Nrf2 却有利于肿瘤发生。由于分子途径的失调以及突变/缺失在肿瘤中很常见，Nrf2 可能是一个有前景的治疗靶点。Nrf2 的过表达可防止肿瘤细胞死亡，并通过提高癌细胞的存活率确保肿瘤发生。此外，Nrf2 的诱导可促进肿瘤细胞的侵袭和转移。Nrf2 的上调刺激上皮-间质转化（EMT）以增加癌症转移。此外，鉴于 Nrf2 的保护功能，其刺激会引发化疗耐药性。天然产物可在癌症治疗中调节 Nrf2 并逆转耐药性。此外，纳米结构可在癌症治疗中特异性靶向 Nrf2 信号通路。本综述讨论了 Nrf2 在增殖、转移和耐药性方面的潜在功能。然后，讨论了天然产物和纳米结构抑制 Nrf2 介导的癌症进展的能力。
