帕尔博西克利布诱导的细胞衰老是由mTOR复合体1和自调节的
Angel Cayo1,2, Whitney Venturini1,2, Danitza Rebolledo-Mira1
1Center for Medical Research, School of Medicine, University of Talca, Talca 3460000, Chile.
International journal of molecular sciences
|June 10, 2023
概括
在衰老细胞中抑制mTORC1矛盾地恶化了与衰老相关的分泌表型 (SASP),但这种效果被抑制自也扭转了,突出了自在SASP调节中的作用.
科学领域:
- 细胞衰老 细胞衰老
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 衰老细胞分泌生物活性分子 (SASP).
- 与衰老相关的自支持通过mTORC1.1通过SASP组件合成.
- mTORC1在CDK4/6抑制剂诱导的衰老中的作用尚不清楚.
研究的目的:
- 调查Palbociclib诱导的衰老中的mTORC1活动.
- 确定单独或与自抑制一起抑制mtORC1对衰老和SASP的影响.
- 评估这些干预措施对SASP的抗瘤潜力的影响.
主要方法:
- 检查了用Palbociclib治疗的AGS和MCF-7细胞.
- 抑制mTORC1和/或自.
- 分析了衰老标志物和SASP组成.
- 评估条件介质对非衰老细胞的影响 (增殖,入侵,迁移).
主要成果:
- 帕尔博西克利布诱导的衰老细胞显示mTORC1活性降低,自性增加.
- 进一步的mTORC1抑制使衰老恶化,由自抑制逆转.
- SASP的组成因mTORC1/自抑制而变化,从而改变了亲瘤原生效应.
结论:
- 帕尔博西克利布诱导的衰老包括mTORC1活动的部分减少和自的上调.
- 自抑制可以抵消mTORC1抑制对衰老的负面影响.
- 通过联合mTORC1和自抑制的SASP调节是自依赖的.
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