由DCA诱导的新陈代谢重编程通过增加胆管癌中线粒体氧化应激来增强西斯丁的敏感性
Hanjiao Qin1, Ge Zheng2, Qiao Li2
1Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, China.
Frontiers in pharmacology
|October 11, 2023
概括
二乙酸盐 (DCA) 通过转移细胞代谢来增强胆瘤的西斯类化疗. 这增加了氧化应激和自,最终抑制了癌细胞的生长,提高了治疗效率.
科学领域:
- 在瘤学瘤学.
- 代谢途径 代谢途径
- 药物耐药性 药物耐药性 药物耐药性
背景情况:
- 胆管癌表现出初级的多药性耐药性,特别是对西斯的耐药性.
- 癌细胞中的高糖分水平与化疗耐药性相关.
- 二乙酸盐 (DCA) 是一种PDK抑制剂,促进线粒体的有氧氧化.
研究的目的:
- 调查DCA在增强胆瘤癌化疗中的作用.
- 探索DCA对细胞代谢和化疗耐药性的影响.
- 阐明DCA与西斯的协同作用背后的机制.
主要方法:
- 通过摄取葡萄糖和乳酸分泌来评估细胞代谢.
- 评估了细胞亡和细胞周期进展.
- 使用Mito-TEMPO来抑制线粒体的活性氧物种 (mtROS).
- 使用PCR阵列和自抑制剂CQ研究细胞应激反应.
主要成果:
- 在西斯普拉丁的压力下,DCA将胆管癌细胞代谢从糖解转移到有氧氧化.
- 通过DCA提高mtROS的代谢重编程,诱导细胞循环停止.
- DCA激活了自和增加了抗氧化剂基因表达.
- 抑制自增强了DCA和西斯的协同作用.
结论:
- 通过增加线粒体氧化应激和抑制细胞生长,DCA增强了胆管癌中西斯丁的敏感性.
- DCA和氨酸 (CQ) 具有协同作用,进一步增加了西斯的敏感性.
- 结合DCA和CQ疗法针对胆管癌的代谢重编程和应激反应途径.
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