建模三维与癌症相关的缓解症和治疗:介素-6传递信号阻断的分子基础和治疗潜力
Marianna Cosentino1, Laura Forcina1, Mariam Zouhair1
1DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy.
Journal of cachexia, sarcopenia and muscle
|September 20, 2023
概括
抑制Interleukin-6 (IL-6) 传递信号有效地对抗癌症缓解症在一个新的肌肉组织模型中. 这种方法保留了肌肉质量和功能,为这种情况提供了一个有前途的治疗策略.
科学领域:
- 生物医学工程 生物医学工程
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 癌症缓解症机制尚不清楚,目前还没有治疗方法来逆转肌肉消耗.
- 介乐-6 (IL-6) 通过不同的信号通路在骨肌肉病理生理学中发挥着关键作用.
研究的目的:
- 使用3Dex vivo肌肉工程组织 (X-MET) 系统来建模与癌症相关的缓解症.
- 为了评估选择性抑制IL-6传递信号在抵消 cachectic 变化的有效性.
主要方法:
- 利用C26腺癌细胞条件介质 (CM) 诱导X-MET.中一个卡塞克特的表型.
- 给药的糖蛋白-130合并的喜梅拉 (gp130Fc) 来中和IL-6的传递信号.
- 评估肌肉质量,肌肉蛋白表达,收缩功能,STAT3信号,以及基因/miRNA表达.
主要成果:
- C26-CM诱导了显著的肌肉质量损失,减少了肌肉素表达,并降低了收缩能力.
- 通过IL-6传输信号激活了STAT3信号,创建了一个前循环.
- gp130Fc治疗防止了STAT3过度激活,保存了肌肉横截面积,并减少了蛋白质分解因子.
- 抑制IL-6的传递信号,使亲细胞灭绝性miRNA表达正常化,并减少了细胞灭绝.
结论:
- 选择性IL-6传递信号抑制是一种有前途的策略,可以对抗癌症缓冲症相关的肌肉变化.
- X-MET模型作为药物查和临床前测试的可靠平台,减少了动物模型的使用.
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