在膀癌中,SRC通过重编程糖解和酸路径,增强了对青的抗药性
Yuwen Gong1, Dongyang Gao1, Yibo Shi1
1Institute of Urology, The Second Hospital of Lanzhou University, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephro-Urological Clinical Center, Lanzhou, Gansu, China.
Communications biology
|January 10, 2025
概括
向SRC通过上调糖解和酸通路来克服膀癌中西斯普拉丁耐药性. 使用eCF506抑制SRC显示抗瘤作用,并在临床前模型中恢复西斯的敏感性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 西斯普拉丁耐药性显著恶化了晚期或复发性膀癌的结果.
- 克服西斯普拉丁耐药性的有效策略仍然有限.
研究的目的:
- 为了研究SRC在膀癌中对西斯普拉丁耐药性的作用.
- 评估SRC抑制作为治疗策略对抗抗西斯普拉丁的膀癌.
主要方法:
- 研究了对抗西斯普拉丁的膀癌细胞中的SRC激活.
- 评估了SRC激活对糖解和酸通路的影响.
- 在体外使用了SRC淘汰和SRC抑制剂 (eCF506).
- 在细胞衍生异种移植 (CDX) 和患者衍生异种移植 (PDX) 模型中评估了eCF506的疗效.
主要成果:
- 确定SRC过度激活是对西斯普拉丁耐药性的关键因素.
- SRC可以调节hexokinase2,增强糖解和酸路径.
- 通过SRC增加的核酸合成和NADPH生产可以中和西斯普拉丁诱导的活性氧物种 (ROS).
- 通过淘汰赛或eCF506抑制SRC可以逆转西斯普拉丁耐药性并减少瘤生长.
- 在CDX和PDX模型中,eCF506显示出显著的抗瘤作用,并恢复了西斯的敏感性.
结论:
- 准SRC是一个有希望的策略,以克服膀癌中西斯普拉丁耐药性.
- SRC抑制为膀癌治疗中的组合疗法提供了潜在的新方法.
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