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Research Article

TRIP13激活糖酵解促进结直肠癌细胞干性增强阿霉素耐药

卷 31, 期 22, 2024

发表于: 12 February, 2024

页: [3397 - 3411] 页: 15

弟呕挨: 10.2174/0109298673255498231117100421

价格: $65

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摘要

背景：化疗耐药是临床化疗失败的主要原因之一。目前的癌症研究正在探索耐药机制和新的治疗靶点。本研究旨在阐明甲状腺激素受体相互作用因子13 (TRIP13)影响结直肠癌(CRC)中阿霉素(DOX)耐药的机制。 方法：利用生物信息学分析明确了TRIP13在结直肠癌组织中的表达，并预测了TRIP13富集途径与糖酵解相关基因和干性指数mRNAsi的相关性。采用实时定量聚合酶链反应和western blot方法分析TRIP13及糖酵解相关基因的表达情况。细胞计数试剂盒-8测定细胞活力和IC50值。Western blot检测干细胞相关因子的表达。细胞功能检测细胞成球能力和糖酵解水平。构建动物模型以确定TRIP13表达对结直肠癌肿瘤生长的影响。 结果：TRIP13在结直肠癌中显著过表达，集中在糖酵解信号通路，且与干性指数mRNAsi呈正相关。高表达的TRIP13促进了结直肠癌中DOX的耐药。进一步的机制研究表明，过表达TRIP13可以通过糖酵解促进细胞的干细胞化，这在动物实验中也得到了证实 结论：TRIP13在结直肠癌中高表达，通过激活糖酵解促进细胞干性，增强结直肠癌细胞对DOX的抗性。这些发现为CRC中DOX耐药的发病机制提供了新的见解，并提示TRIP13可能是逆转CRC中DOX耐药的新靶点。

关键词: TRIP13，糖酵解，干性，结直肠癌，阿霉素耐药，生物信息学分析。

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