Nrf2信号在铁死亡激活的癌症治疗中的调节和功能。
The regulation and function of Nrf2 signaling in ferroptosis-activated cancer therapy.
发表日期:2024 Jul 17
作者:
Xin Jiang, Min Yu, Wei-Kai Wang, Li-Yuan Zhu, Xian Wang, Hong-Chuan Jin, Li-Feng Feng
来源:
ACTA PHARMACOLOGICA SINICA
摘要:
铁死亡是一种铁依赖性程序性细胞死亡过程,涉及通过芬顿反应进行脂质氧化,产生脂质过氧化物,导致脂质双层破坏,而脂质双层对于细胞生存至关重要。铁死亡与多种癌症的发生和治疗反应有关,靶向铁死亡已成为一种有前景的癌症治疗策略。然而,癌细胞可以通过激活或重塑各种信号通路(包括氧化应激通路)来逃避细胞铁死亡,从而限制铁死亡激活靶向治疗的功效。关键的抗氧化转录因子,核因子 E2 相关因子 2(Nrf2 或 NFE2L2),通过重新编程铁、中间体和谷胱甘肽过氧化物酶 4 (GPX4) 相关网络和抗氧化系统来减弱防御机制,从而在防御机制中发挥主导作用。铁死亡。在这篇综述中,我们总结了 Nrf2 信号在铁死亡激活癌症治疗中的调控和功能的最新进展,并探讨了将 Nrf2 抑制剂和铁死亡诱导剂结合起来作为一种有前途的癌症治疗策略的前景。© 2024。作者,经中国科学院上海药物研究所和中国药理学会独家授权。
Ferroptosis is an iron-dependent programmed cell death process that involves lipid oxidation via the Fenton reaction to produce lipid peroxides, causing disruption of the lipid bilayer, which is essential for cellular survival. Ferroptosis has been implicated in the occurrence and treatment response of various types of cancer, and targeting ferroptosis has emerged as a promising strategy for cancer therapy. However, cancer cells can escape cellular ferroptosis by activating or remodeling various signaling pathways, including oxidative stress pathways, thereby limiting the efficacy of ferroptosis-activating targeted therapy. The key anti-oxidative transcription factor, nuclear factor E2 related factor 2 (Nrf2 or NFE2L2), plays a dominant role in defense machinery by reprogramming the iron, intermediate, and glutathione peroxidase 4 (GPX4)-related network and the antioxidant system to attenuate ferroptosis. In this review, we summarize the recent advances in the regulation and function of Nrf2 signaling in ferroptosis-activated cancer therapy and explore the prospect of combining Nrf2 inhibitors and ferroptosis inducers as a promising cancer treatment strategy.© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.