由ITCH调解的FOLR1通过抑制鼻癌中 Pyroptosis 来促进帕克利塔塞尔耐药性
Gehou Zhang1, Yexun Song1, Honghui Liu1
1Department of Otolaryngology, The Third Xiangya Hospital of Central South University, Changsha City, Hunan Province, China.
Archiv der Pharmazie
|February 4, 2026
概括
叶酸受体1 (FOLR1) 通过抑制 pyroptosis 在鼻癌 (NPC) 中促进包素耐药性. 向FOLR1可能会改善NPC患者的化疗效果.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 帕克利塔塞尔是用于鼻癌 (NPC) 的关键化疗.
- 瘤细胞对帕克利塔塞尔的耐药性是NPC治疗的一个主要障碍.
- 叶酸受体1 (FOLR1) 在NPC中帕克利塔塞尔耐药性的作用尚不清楚.
研究的目的:
- 调查FOLR1对NPC细胞中帕克利塔塞尔耐药性的影响.
- 为了阐明FOLR1-介导化学抵抗的潜在机制.
- 评估在NPC中准FOLR1的治疗潜力.
主要方法:
- 定量实时PCR (RT-qPCR) 和FOLR1表达的西部涂抹.
- 细胞计数工具-8 (CCK-8) 试验用于IC50的确定.
- EdU,殖民地形成,流细胞计,免疫光和共同免疫沉 (Co-IP) 测试.
- 在裸体小鼠中的NPC异种移植模型.
主要成果:
- 在NPC中,FOLR1过度表达,并与预后不佳有关.
- 升高的FOLR1表达和低的烧灭水平与帕克利塔塞尔耐药性相关.
- 抑制FOLR1降低了化学阻力,而其过度表达则通过抑制NLRP3依赖性热,增加了耐药性.
- ITCH促进了FOLR1的降解,从而降低了化学电阻.
- 通过mTOR途径和自,FOLR1抑制了热.
结论:
- 过度表达FOLR1通过NLRP3信号通路抑制热致死,从而促进NPC中的帕克利塔塞尔耐药性.
- 针对FOLR1,可能通过增强ITCH介导的降解,可以克服化学阻力.
- 减少FOLR1的表达增强了帕克利塔塞尔的敏感性,并抑制了瘤的生长.
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