获得了对维穆拉芬尼的耐药性通过抑制STAT3激活来抑制甲状腺癌干细胞自我更新
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Updated: May 20, 2025

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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
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Yuqing Zhao1, Yurong Lu1, Wei Li2
1Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, PR China.
Cellular signalling
|May 9, 2025
概括
适应Vemurafenib (PLX4032) 的甲状腺癌细胞显示自我更新能力降低. 这种药物耐药性与STAT3激活受损和关键干性基因的表达降低有关.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 维穆拉芬尼 (PLX4032),是一种B-Raf激酶抑制剂,对黑色素瘤有效,但对甲状腺癌不有效.
- 癌症干细胞 (CSCs) 与药物耐药性 (DR) 有关.
- 这项研究调查了PLX4032-耐药性厌塑性甲状腺癌 (ATC) 中的CSC.
研究的目的:
- 为了确定甲状腺癌细胞中CSCs的特征,这些细胞获得了对PLX4032.2的适应性耐药性.
- 阐明这种抗性背后的分子机制及其对茎状性的影响.
主要方法:
- 通过长时间的药物暴露,建立了一个抗PLX4032的ATC细胞系 (SW1736).
- 分析了HER3,YAP,MAPK,PI3K,SOCS3和STAT3通道的表达.
- 评估了干性标记物 (Gli1,BMI1,SOX2),甲状腺球形成,ALDH活性和瘤异种移植潜力.
- 使用STAT3淘汰和鲁克索利提尼布 (JAK抑制剂) 来研究STAT3信号.
主要成果:
- DR细胞表现出高的HER3,YAP,MAPK和PI3K通路激活,但自我更新能力降低.
- DR细胞显示干基因 (Gli1,BMI1,SOX2) 的表达减少,甲状腺球减少,ALDH活性降低.
- 构成性ERK的激活导致SOCS3的上调,抑制STAT3的激活.
- STAT3抑制降低了干性标记物;STAT3过度表达增加了它们.
结论:
- 适应PLX4032的甲状腺癌细胞显示有限的自我更新.
- 损坏的STAT3激活和减少的干性基因表达是这种适应性抵抗的关键特征.
- 准STAT3信号可能为PLX4032抗性甲状腺癌提供治疗策略.
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