在癌症和瘤基因诱导的衰老中,REV-ERBs的药理活性是致命的
Gabriele Sulli1, Amy Rommel2, Xiaojie Wang3
1Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Nature
|January 11, 2018
概括
通过破坏昼夜节律,REV-ERB激动剂SR9009和SR9011可以选择性地杀死癌细胞,从而提供一种新的治疗策略. 这些化合物表现出强烈的抗癌作用,而不会伤害正常细胞.
科学领域:
- 时间生物学
- 分子瘤学
- 药理学
背景情况:
- 循环时钟的破坏与癌症的发展有关.
- 药物针对性对生物节律机制是一种潜在的癌症治疗方法.
- REV-ERB核受体是生物钟的关键组成部分.
研究的目的:
- 研究REV-ERB激动剂的抗癌潜力.
- 确定REV-ERB激动剂的作用机制和选择性.
- 在临床前模型中评估REV-ERB激动剂的疗效和毒性.
主要方法:
- 用REV-ERB激活剂SR9009和SR9011治疗癌细胞和正常细胞
- 细胞活性的评估,细胞亡,自和新生脂质生成.
- 使用小鼠质母细胞瘤模型的体内研究.
主要成果:
- 在癌细胞和衰老细胞中,SR9009和SR9011可选择性地诱导细胞亡,而不会影响正常细胞.
- 在各种癌症驱动因素,p53缺乏和缺氧条件中观察到抗癌活性.
- REV-ERB激动剂抑制自和新生脂质生成,导致癌细胞死亡.
- 在体内,这些激动剂减少了质母细胞瘤的生长,并改善了生存率,没有明显的毒性.
结论:
- REV-ERB激动剂代表了一类有前途的抗癌药物,对瘤具有选择性毒性.
- 生物节律调节剂的药理调节提供了有效的抗瘤策略.
- REV-ERB激动剂具有广泛的治疗窗口和治疗各种癌症的潜力.
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