Erk1/2 在肝细胞癌中编排SSPH I诱导的氧化应激,线粒体功能障碍和铁亡
Yuewen Sun1, Ying Zhou1, Dan Huang2
1Guangxi University of Chinese Medicine, Nanning, China.
Journal of cellular and molecular medicine
|May 20, 2025
概括
类固醇沙素SSPH I通过激活Erk1/2信号传递来诱导肝细胞癌 (HCC) 细胞死亡,从而放大氧化应激和铁亡. 在这个过程中,Erk1/2充当了中央调节器,突出显示了它对HCC的治疗潜力.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 肝细胞癌 (HCC) 涉及Erk1/2信号传递,反应性氧物种 (ROS) 和铁代谢之间的复杂相互作用.
- 类固醇香SSPH I是一种已知的铁灭诱导剂,通过Erk1/2和ROS途径对双重药理效应的理解不佳.
研究的目的:
- 调查Erk1/2在HCC中的铁和氧化应激中的调节作用.
- 分析HCC中的Erk1/2上的铁和氧化应激的反机制.
- 在体外和体内阐明SSPH I的抗HCC作用和机制.
主要方法:
- 使用了U0126 (Erk1/2抑制剂),费罗斯塔丁-1 (ferroptosis抑制剂) 和N-乙半氨酸 (ROS清除剂) 与SSPH I.
- 评估了对细胞活力,线粒体动力学,铁亡和氧化应激的影响.
- 使用细胞和动物模型进行机械和体内研究.
主要成果:
- SSPH I 破坏了线粒体功能,并通过铁积累和ROS生成抑制了HCC细胞生存,激活了Erk1/2.2.
- Erk1/2抑制完全取消了SSPH I介导的铁和Nrf1/2-HO-1轴调节.
- 结合的SSPH I和U0126对异种移植生长产生了对抗作用,与单一疗法不同.
结论:
- Erk1/2激活是驱动SSPH I诱导的氧化应激,线粒体功能障碍和HCC中的铁亡的中心机制.
- SSPH I通过Erk1/2-介导的铁灭诱导表现出抗HCC作用.
- 准Erk1/2通路为HCC提供了潜在的治疗策略.
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