常胺对昼夜基因表达和同步Caco-2细胞中的细胞命运的影响
Dilek Ozturk Civelek1, Beyza Goncu2, Sadullah Goncu3
1Istanbul University-Cerrahpasa, Faculty of Pharmacy, Department of Pharmacology, Istanbul, Turkiye; Bezmialem Vakif University, Faculty of Pharmacy, Department of Pharmacology, Istanbul, Turkiye.
Experimental cell research
|November 14, 2025
概括
作为一种mTOR抑制剂的Everolimus会影响昼夜基因表达,并对结直肠癌细胞的细胞活力和细胞亡产生时间依赖的影响. 这表明昼夜定时可能会增强针对mTOR的治疗方法.
科学领域:
- 时间生物学 时间生物学
- 癌症生物学 癌症生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 昼夜节律对细胞增殖和新陈代谢至关重要,它们的干扰与结直肠癌 (CRC) 有关.
- 拉巴胺素 (mTOR) 信号通路的机械性标与昼夜时钟相互作用,但其抑制对肠道模型中时钟基因动态的影响尚未完全理解.
研究的目的:
- 研究一种mTOR抑制剂Everolimus对昼夜基因表达,细胞活力,细胞亡和细胞周期进展的影响.
- 在同步的Caco-2细胞中分析这些效应,考虑细胞汇合和昼夜时间 (CT).
主要方法:
- 在多个昼夜时间 (CT6-CT60) 中同步和采样Caco-2细胞.
- 使用qRT-PCR测量了BMAL1,PER2和mTOR的基因表达.
- 细胞活力,细胞亡和细胞循环被评估使用MuseTM细胞分析仪在治疗everolimus后.
主要成果:
- 埃弗罗利斯 (50μM) 显著降低了细胞活力,并以时间依赖的方式增加了细胞亡,CT6和CT18的效果最大.
- 药物敏感性由昼夜时间调节,在CT6观察到亡的增加.
- 埃弗罗利斯改变了BMAL1和PER2的表达节奏,并减少了mTOR的表达,特别是当基线mTOR水平最高时.
结论:
- 埃弗罗利斯影响昼夜基因表达,并在Caco-2细胞中表现出时间依赖的抗增殖和亲亡效应.
- 这些发现突出了利用昼夜定时的潜力,以优化对结直肠癌的mTOR向疗法.
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