在肺腺癌中,CC-115通过Akt/Bax路径调解了GSDME依赖性 Pyroptosis
Ting Zhang1, Ming-Quan Liu1, Guang-Su Xie2
1School of Clinical Medicine & The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, China.
Journal of Cancer
|June 7, 2023
概括
新型化合物CC-115在肺腺癌细胞中触发了被编程的细胞死亡,称为热致死. 这一发现突出了CC-115作为肺癌潜在的新疗法,克服化疗耐药性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞死亡研究 细胞死亡研究
背景情况:
- 化疗是对肺癌等固体瘤的主要治疗方法,但耐药性限制了其有效性.
- 新型治疗策略对于克服肺腺癌 (LUAD) 中的化疗耐药性至关重要.
- 新型化合物CC-115对LUAD的疗效在很大程度上仍未被探索.
研究的目的:
- 为了研究CC-115在肺腺癌 (LUAD) 中的抗瘤作用.
- 为了阐明在LUAD中CC-115诱导的细胞死亡的机制.
- 评估CC-115作为LUAD的潜在治疗剂.
主要方法:
- 在CC-115处理A549和H1650LUAD细胞系.
- 对细胞死亡形态和机制的分析,包括热.
- 研究DNA-PK,mTOR,Akt,Bax和gasdermin E (GSDME) 在CC-115的行动中的作用.
- 在异种移植小鼠模型中进行评估.
主要成果:
- CC-115诱导了类似于 LUAD 细胞中 pyroptosis 的细胞死亡.
- CC-115作为DNA-PK和mTOR的双重抑制剂,激活了GSDME介导的热.
- 该化合物抑制了Akt酸化,促进了巴克斯介导的线粒体通路激活.
- 在体内,CC-115治疗上调了Bax和GSDME-N的表达,并减少了瘤的大小.
结论:
- CC-115通过通过Akt/Bax-线粒体内在途径诱导GSDME介导的烧,抑制LUAD瘤的生长.
- CC-115显示出作为治疗肺腺癌的治疗剂的巨大潜力.
- 这些发现为CC-115在克服化疗耐药性的有效性提供了机制基础.
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