过氧酸盐与Sorafenib在肝癌细胞中诱导的线粒体功能障碍有关
Patricia de la Cruz-Ojeda1, Elena Navarro-Villarán1, Marina Fuertes-Agudo2
1Institute of Biomedicine of Seville (IBiS), Hospital University "Virgen Del Rocío"/CSIC/University of Seville, Seville, Spain; Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain; Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain.
索拉芬尼因增加氧化应激和损害线粒体而导致肝癌细胞死亡. 过氧化生成破坏了电子运输链的功能,影响了细胞的存活.
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:
- 索拉菲尼布是一种用于晚期肝细胞癌 (HCC) 的氨酸激酶抑制剂 (TKI).
- 索拉费尼布诱导的细胞死亡与肝癌细胞中的线粒体功能障碍有关.
- 氧化和化压力与Sorafenib对线粒体的影响有关.
研究的目的:
- 为了研究氧化和化应激在肝癌细胞中索拉费尼布诱导的线粒体功能障碍中的作用.
- 阐明Sorafenib对线粒体呼吸和电子运输链 (ETC) 的影响.
主要方法:
- 用Sorafenib和诸如MnTBAP,catalase和FeTPPs之类的药物治疗了HepG2细胞.
- 测量了氧气消耗,糖分流和线粒体复合体活动.
- 使用免疫块和RNA序列分析ETC子单元的蛋白质和mRNA表达.
主要成果:
- 索拉费尼布 (10μM) 增加了氧化和超氧化,产生过氧,并降低了氧气消耗.
- 观察到线粒体网络的混乱和膜潜力的损失.
- FeTPPs治疗部分恢复了线粒体功能和ATP生产.
- 索拉芬尼降低了线粒体和核编码ETC子单元的调节,影响复合体I,III和IV蛋白表达和复合体I活性.
- 糖解变化,克雷布斯循环中间体减少,NAD/NADH比率增加.
结论:
- 肝癌中索拉费尼布诱导的细胞死亡与过氧酸盐生成有关.
- 过氧酸盐会影响ETC子单元的表达和线粒体的功能.
- 向过氧酸盐可能为Sorafenib治疗的HCC提供治疗策略.
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