奥兰沙平抑制了mPFC活动 - - 上腺素释放以缓解慢性压力下CLOCK增强的癌症干
Jinxin Lu1,2, Xiaoyu Zhang1, Keyu Su1,3
1Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
Cell communication and signaling : CCS
|July 25, 2024
概括
奥兰zapine (OLZ) 通过抑制mPFC-NE-CLOCK轴逆转慢性压力诱导的肺瘤发生和化学抵抗. 这种干预减少了类似焦虑的行为和癌症的根性,提供了一个新的治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 慢性压力通过神经内分泌路径加剧癌症的发展.
- 大脑与身体相互作用影响压力诱导的瘤发生的精确机制尚未完全理解.
- 已知 olanzapine (OLZ) 可以逆转与慢性压力相关的焦虑.
研究的目的:
- 为了研究 olanzapine (OLZ) 对慢性压力诱导的肺瘤发生和癌症干的作用.
- 阐明涉及神经内分泌激活的潜在脑体相互作用机制.
- 在肺癌模型中评估OLZ对焦虑类行为和化疗敏感性的影响.
主要方法:
- 使用了KrasLSL-G12D/WT和LLC1同源性肺癌模型.
- 通过qPCR,西部涂抹,免疫组织学和流动细胞计量评估癌症干细胞标志物.
- 通过高加迷宫和开放场地测试评估类似焦虑的行为;通过尾部悬挂测试评估类似抑郁的行为.
- 使用医院焦虑和抑郁量表 (HADS) 评估人类的焦虑和抑郁.
- 在体内和体外评估的化学敏感性.
主要成果:
- 在这两种模型中, olanzapine (OLZ) 逆转了慢性压力增强的肺瘤发生.
- 通过抑制mPFC神经活性和减少北上腺素 (NE) 释放,OLZ减轻了焦虑和类似抑郁的行为.
- NE激活了ADRB2-cAMP-PKA-CREB通路,促进了CLOCK转录和癌症干性.
- 时钟缺陷或OLZ逆转了NE/慢性压力诱导的凝抗药.
- 瘤时钟表达与肺癌患者的压力,NE水平和不良预后相关.
结论:
- 奥兰zapine (OLZ) 通过一种新的机制改善慢性压力诱导的瘤发生和化学抵抗.
- OLZ抑制mPFC-NE-CLOCK轴,扭转压力诱导的焦虑类行为和肺癌干细胞.
- 减少NE释放抑制ADRB2-cAMP-PKA-CREB通路,降低CLOCK转录和克服化学抵抗.
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