Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
Biochem Biophys Res Commun. 2023 Sep 3;671:225-228. doi: 10.1016/j.bbrc.2023.06.022. Epub 2023 Jun 7.
Ferroptosis is a recently identified type of regulated cell death characterized by lipid peroxidation and redox-active iron accumulation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial regulator of genes involved in glutathione biosynthesis, antioxidant responses, lipid metabolism, and iron metabolism, contributing to the evasion of ferroptosis. Inhibiting the Nrf2 pathway has been shown to sensitize cancer cells to ferroptosis. In head and neck cancer cells, we found that activation of the Nrf2-antioxidant responsive element pathway leads to ferroptosis resistance, and inhibiting this pathway reverses ferroptosis evasion. Our study suggests that modulating the Nrf2 pathway could be a promising strategy to overcome resistance in cancer therapy for head and neck cancer. Further research is required to investigate the potential of ferroptosis induction in therapy-resistant head and neck cancer. Targeting Nrf2 through ferroptosis-based cancer therapy may be a novel and effective approach to reverse the resistance of head and neck cancer therapy.
铁死亡是一种新近发现的受调控的细胞死亡方式，其特征为脂质过氧化和氧化还原活性铁的积累。核因子红细胞 2 相关因子 2（Nrf2）是参与谷胱甘肽生物合成、抗氧化反应、脂质代谢和铁代谢的基因的关键调节剂，有助于逃避铁死亡。抑制 Nrf2 途径已被证明可使癌细胞对铁死亡敏感。在头颈部癌细胞中，我们发现 Nrf2-抗氧化反应元件途径的激活导致铁死亡抵抗，抑制该途径可逆转铁死亡逃避。我们的研究表明，调节 Nrf2 途径可能是克服头颈部癌症治疗中耐药性的一种有前途的策略。需要进一步研究铁死亡诱导在治疗耐药性头颈部癌症中的潜力。通过基于铁死亡的癌症治疗靶向 Nrf2 可能是一种新颖而有效的方法，可逆转头颈部癌症治疗的耐药性。
