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酸化取代了分子异质性,在结肠癌中形成了可治疗向的代谢表型
Elena Richiardone1, Maria Virginia Giolito1, Rim Al Roumi1
1Pole of Pharmacology and Therapeutics (FATH), Institut de Recherche Expérimentale et Clinique (IREC), UCLouvain, Avenue Hippocrate 57, B1.57.04, B-1200, Brussels, Belgium.
Cancer letters
|February 3, 2025
概括
结直肠癌细胞适应酸性条件导致代谢转变,增加对PHGDH的依赖. 抑制PHGDH或呼吸有效减缓瘤生长,提供一种潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 癌症新陈代谢 癌症新陈代谢
- 瘤微环境 瘤微环境
背景情况:
- 大肠直肠癌 (CRC) 呈现出显著的异质性,使患者管理复杂化.
- 瘤微环境 (TME),特别是酸化,驱动癌细胞的可塑性和进展.
- 酸性状况是固体瘤的常见标志,促进了侵略性的表型.
研究的目的:
- 为了研究结直肠癌细胞对长期酸性pH暴露的代谢适应.
- 评估向化适应的CRC细胞中的特定代谢途径的治疗潜力.
主要方法:
- 不同质的CRC细胞长期适应酸性pH.
- 分析代谢变化,包括糖解和呼吸.
- 药理上抑制糖酸脱酶 (PHGDH) 和线粒体呼吸.
- 在2D,3D培养和患者衍生器官中对细胞生长抑制的评估.
主要成果:
- 酸性pH适应诱导了常见的代谢变化,包括糖解-呼吸开关.
- 在酸性条件下,CRC细胞对糖酸脱酶 (PHGDH) 活性的依赖性增加.
- 抑制PHGDH或线粒体呼吸显著抑制了暴露于酸性酶的CRC细胞和器官的生长.
结论:
- 准PHGDH或线粒体呼吸是结直肠癌的一个有前途的治疗策略.
- 利用酸性瘤微环境可以提供一种"适合所有人"的方法来延迟CRC进展.
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