拉福克萨尼德通过VDAC1调节在结直肠癌细胞中破坏线粒体平衡
Lorenzo Tomassini1, Teresa Pacifico1, Mattia Alberto Serra1
1Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Cell death discovery
|March 5, 2026
概括
拉福克桑胺通过抑制呼吸和增加活性氧物种来破坏结直肠癌 (CRC) 细胞中的线粒体功能,导致细胞死亡. 这项研究揭示了其用于治疗CRC的机制.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 线粒体对于癌细胞生存和新陈代谢至关重要.
- 准线粒体平衡是一种有前途的癌症治疗策略.
- 拉福克桑胺是一种杀虫剂,在结直肠癌 (CRC) 中表现出抗瘤活性,但其机制尚不清楚.
研究的目的:
- 研究rafoxanide对CRC细胞中的线粒体功能和应激反应的影响.
- 阐明拉福克桑胺抗瘤作用背后的分子机制.
主要方法:
- 使用了转录组,蛋白组和代谢组分析.
- 评估了线粒体呼吸,膜潜力和反应性氧物种的产生.
- 检查了CRC细胞系,小鼠CRC模型和人类CRC实验对象的影响.
主要成果:
- 拉福克萨尼德损害了线粒体呼吸和分散了膜潜能.
- 它诱导了持续的线粒体功能障碍,代谢失败和细胞染色体c释放.
- 抑制呼吸链复合体I和III增加了活性氧物种,促进了VDAC1的寡合化和外膜透.
- 拉福克桑胺在体外,体内和体外系统中始终改变了线粒体功能.
结论:
- 拉福克桑胺调节了CRC细胞中的线粒体平衡.
- 它诱导了依赖于氧化还原的VDAC1激活和渐进的线粒体功能障碍.
- 提供了对rafoxanide抗瘤活性的机械洞察力,并支持探索用于CRC治疗的线粒体应激调制.
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