结肠瘤细胞死亡导致mTOR依赖性
Mark Schmitt1,2,3, Fatih Ceteci1,2, Jalaj Gupta1,2,4
1Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, Frankfurt am Main, Germany.
Nature
|November 17, 2022
概括
死亡的癌细胞通过ATP释放和P2X4受体激活引发邻近瘤细胞的生存途径. 这为mTOR抑制剂造成了脆弱性,为固体瘤提供了新的联合治疗策略.
科学领域:
- 癌症学
- 细胞生物学
- 分子医学
背景情况:
- 固体瘤通过细胞死亡和增殖的平衡来维持生长.
- 死亡的癌细胞可以在瘤微环境中激活前瘤修复程序.
- 癌细胞死亡对邻近的瘤细胞和治疗耐药性的直接影响尚不清楚.
研究的目的:
- 研究化疗引起的癌细胞死亡对邻近瘤上皮质的直接影响.
- 阐明死亡细胞导致治疗耐药性的机制.
- 确定组合疗法的潜在治疗点.
主要方法:
- 使用来自患者的结直肠瘤器官.
- 研究了ATP释放,P2X4受体激活和mTOR信号通路.
- 评估了活性氧物种 (ROS) 和DNA损伤的作用.
- 评估的组合疗法包括化疗,P2X4抑制和mTOR阻塞.
主要成果:
- 化学疗法诱导的细胞死亡释放ATP,激活P2X4受体和邻近癌细胞的mTOR依赖生存计划.
- 这创造了一个
- mTOR成情况
- 由于ROS的产生和DNA的损伤,在存活的细胞中.
- 抑制P2X4或mTOR与化疗协同作用,导致显著的细胞死亡和瘤回归.
- 清理ROS可以避免依赖mTOR激活.
结论:
- 死亡的癌细胞在存活的瘤细胞中依赖于抗亡途径.
- 针对P2X4受体或mTOR通路与化疗一起提供了一个有前途的组合治疗策略.
- 这种方法特别适用于表达P2X4的上皮瘤.
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