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转录基因分析揭示了NRF2介导的氧化和代谢重编程在抗索拉芬尼布的肝细胞癌细胞中

Angelo Michilli¹, Cristian Bassi^2,3, Farzaneh Moshiri²

¹Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy.

Biotech (Basel (Switzerland))

|February 20, 2026

概括

肝细胞癌 (HCC) 中的索拉芬尼抗性涉及NRF2驱动的代谢变化,促进抗氧化防御和生存. 针对这些NRF2通路可以克服HCC患者的索拉芬尼抗性.

科学领域:

肝细胞癌研究肝细胞癌研究
癌症药物耐药性机制癌症药物耐药性机制
分子瘤学分子瘤学

背景情况:

索拉费尼布是晚期肝细胞癌 (HCC) 的关键治疗方法,治疗不适合免疫治疗的患者.
获得的耐药性限制了索拉费尼布的长期疗效,其分子驱动因素尚未完全理解.

研究的目的:

研究HCC.中获得的索拉芬尼布耐药性背后的分子机制.
确定关键的分子途径和潜在的治疗点,以克服索拉尼布耐药性.

主要方法:

建立了获得索拉费尼布耐药性的小鼠模型.
在对索拉芬尼布敏感和耐药的HCC细胞上进行了比较RNA测序.
使用路径分析和基因组丰富分析 (GSEA).
通过药理抑制研究了与核因素红色素2相关的因子2 (NRF2) 的作用.

主要成果:

在HCC细胞中发现了一种独特的1264基因抗药特征.
观察到代谢和细胞间信号通路的下调.
发现显著上调氧化还原调节,线粒体和细胞应激反应程序.
证明了NRF2调节基因的上调,这些基因参与了抗氧化剂防御和ferroptosis抑制.
表明NRF2抑制恢复了索拉芬尼的敏感性.

结论:

在HCC中获得的索拉芬尼抗性具有稳定的NRF2驱动的转录和代谢重编程的特征.
这种重编程增强了抗氧化能力,抑制了铁亡,并促进了瘤细胞的存活.
准NRF2调节的氧化还原代谢是一个有前途的策略,以克服HCC中索拉芬尼抗性.

关键词:

这就是NRF2的NRF2.肝细胞癌是肝细胞癌.氧化应激是一种氧化应激.氧化还原代谢氧化还原代谢索拉费尼布耐药性索拉费尼布耐药性转录组学转录组学是指转录组学.

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