缺少PEX5通过MGST1-GSH排毒功能增强放射敏感性,并促进肝癌中的铁亡
Zhuhui Yuan1, Tong Liu2, Ping Jiang1
1Department of Radiation Oncology, Cancer Center of Peking University Third Hospital, Peking University Third Hospital, Beijing, 100191, China.
Science China. Life sciences
|July 4, 2025
概括
肝癌细胞通过谷氨 (GSH) 抵抗辐射诱导的铁亡. 抑制PEX5会损害GSH排毒,增强铁亡和辐射损伤,提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 肝癌表现出对放射治疗的耐药性,部分由铁和谷氨 (GSH) 介导.
- 氧体受PEX5 (氧体生物发生基因5) 调节,在氧化还原平衡中起作用,但PEX5对GSH介导的铁灭抵抗的影响尚不清楚.
研究的目的:
- 调查PEX5在调节肝癌中GSH介导的耐辐射诱导铁亡的作用.
- 阐明PEX5影响铁和辐射敏感性的潜在机制.
主要方法:
- 利用有针对性的代谢学,RNA测序和拉曼光谱学.
- 对抗辐射肝癌细胞模型,人类肝癌器官和小鼠模型进行了实验.
主要成果:
- 结合铁致死诱导剂和放射治疗 (IR) 克服了放射电阻.
- 增加的GSH合成与IR诱导的铁灭抵抗相关;外源的GSH强化抵抗.
- PEX5抑制逆转了GSH介导的抗性,通过损害MGST1-GSH解毒路径来增强铁和辐射损伤.
结论:
- 缺少PEX5会通过破坏MGST1-GSH解毒路径和氧化还原平衡来增强铁和辐射引起的损伤.
- 这项研究揭示了PEX5在过氧体介导铁亡中的新功能,表明PEX5是提高放射治疗疗效的潜在治疗标.
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