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在三阴性乳腺癌中GPX4抑制剂耐药性和转移性特征

Marie Sabatier¹, Mayher Kaur¹, Milena Chaufan¹

¹Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|February 18, 2026

概括

产生对RSL3和ML210等铁灭抑制剂的耐药性会改变癌细胞代谢和上皮特征,根据传播途径对转移产生不同的影响.

科学领域:

在瘤学瘤学.
癌症生物学癌症生物学
转移研究研究转移研究

背景情况:

铁灭诱导是一种使用小分子调节器的有前途的癌症治疗策略.
谷氨过氧化酶4 (GPX4) 抑制剂 (例如RSL3,ML210) 通过中和脂质过氧化物来诱导铁.
关于GPX4抑制剂耐药性在癌症转移中的作用的知识有限.

研究的目的:

为了研究适应GPX4抑制的癌细胞的转移潜力.
描述GPX4抑制剂耐药 (GPX4i) 癌细胞中的代谢和表型变化.

主要方法:

三重阴性乳腺癌细胞系 (M231,4T1) 用GPX4抑制剂进行培养,以产生耐药细胞系 (GPX4i).
分析了来自GPX4i耐药细胞和亲细胞的瘤的代谢和脂质学概况.
评估了表皮样标记物 (vimentin, EpCAM) 的变化.
用自发和静脉输入转移模型来评估转移负担.

主要成果:

与父母瘤相比,GPX4i耐药瘤表现出不同的代谢和脂质组概况.
对GPX4抑制剂的耐药性诱导了转向类似上皮质的状态 (减少维丁,增加EpCAM).
抗GPX4i细胞从原发性瘤中形成的自发性转移较少.
在静脉注射后,没有观察到总体转移负担的显著差异.

结论:

长期在体外暴露于GPX4抑制剂会导致癌细胞表型的显著改变.
抗GPX4抑制剂的耐药性影响癌细胞的转移行为,特别是自发转移.
这些发现凸显了铁灭抵抗和癌症传播之间的复杂相互作用.

关键词:

铁性化 (ferroptosis) 是一种脂质过氧化过氧化发生转移的转移.瘤微环境是一个微环境.

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