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老化剂对SASP细胞因子分泌和CAFs对EMT的调节的差异性影响

Daria A Bogdanova^1,2, Ekaterina D Kolosova², Tamara V Pukhalskaia^1,2

¹Division of Immunobiology and Biomedicine, Sirius University of Science and Technology, Sirius, Krasndarsky Krai, 354340 Sochi, Russia.

International journal of molecular sciences

|April 13, 2024

概括

针对瘤微环境中的衰老细胞的老化药物可以产生相反的效果. 矛盾的是,一些老化药物可能会促进瘤的进展和对治疗的抗性.

科学领域:

在瘤学瘤学.
细胞生物学细胞生物学
药理学药理学是指药理学的学科.

背景情况:

瘤微环境 (TME) 对瘤进展和治疗反应至关重要.
细胞衰老及其相关的分泌表型 (SASP) 可以影响瘤发生.
老化疗法旨在消除衰老细胞,提供一种新的抗癌策略.

研究的目的:

研究两种老化药物 - - 纳维托克拉克斯和达沙替尼/克尔塞丁 - - 对癌症相关纤维细胞 (CAFs) 的差异作用及其在上皮-介质细胞过渡 (EMT) 中的作用.
评估老化疗法超越老化细胞枯竭的潜在副作用.

主要方法:

癌症相关纤维细胞 (CAFs) 用纳维托克拉克斯或达沙替尼/克尔塞丁治疗.
衰老细胞减少的量化.
对老化相关分泌表型 (SASP) 组件的分析,特别是IL-6分泌.
在MC38结肠直肠癌细胞中评估表皮-介质细胞过渡 (EMT) 和细胞迁移.

主要成果:

纳维托克拉克斯和达沙替尼/奎尔塞丁都有效地减少了老化的CAF.
与纳维托克拉克斯不同,达沙替尼/克尔塞丁增加了CAFs的IL-6分泌.
这种IL-6的增加与MC38癌细胞的增强迁移和EMT相关.

结论:

老化药物可以对CAF和促进瘤的过程产生明显的,甚至相反的效果.
一些老化剂可能具有促进瘤发生的副作用,独立于它们的老化活性.
在临床应用之前,需要对老化剂进行广泛的临床前评估,以了解它们对瘤进展和治疗耐药性的多方面的影响.

关键词:

与癌症相关的纤维细胞 (CAFs).结肠直肠癌是什么意思表皮介酶过渡 (EMT) 发生.互白素-6 (IL-6) 是一种蛋白质.衰老是一种老化.与衰老相关的分泌表现型 (SASP)

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