用ROS为燃料的盟友:STAT3,PKM2和HIF-1α影响激素独立癌症中的能量代谢
Sara Fiorini1, Bruno Maras1, Giuseppina Mignogna1
1Department of Biochemical Science "A. Rossi Fanelli", Faculty of Pharmacy and Medicine, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
International journal of molecular sciences
|March 14, 2026
概括
在激进的无激素乳腺癌和前列腺癌中,代谢重编程是由STAT3-PKM2-HIF-1α/ROS轴驱动的. 准这种途径会改变新陈代谢,减少氧化应激,并损害癌细胞生长.
科学领域:
- 在瘤学瘤学.
- 癌症新陈代谢 癌症新陈代谢
- 分子生物学分子生物学
背景情况:
- 激素独立的乳腺癌和前列腺癌表现出侵略性行为,代谢重编程和对内分泌疗法的耐药性.
- 瘤进展与基因调节和能量代谢连接的信号网络维持的代谢可塑性有关.
- 由活性氧物种 (ROS) 增强的STAT3-PKM2-HIF-1α轴与华堡效应和细胞适应有关.
研究的目的:
- 研究STAT3-PKM2-HIF-1α/ROS轴在荷尔蒙独立癌症中的作用.
- 探索针对这一轴对癌细胞代谢和表型的影响.
主要方法:
- 使用了与雄激素独立的前列腺癌 (DU145) 和三阴性乳腺癌 (KPL-4) 细胞系.
- 药理上抑制STAT3,L-氨酸稳定PKM2,N-乙半氨酸用于ROS清理.
- 评估了分子变化 (STAT3酸化,PKM2转位,HIF-1α稳定),代谢参数 (ROS,乳酸盐,酸盐,氧化酸化) 和功能结果 (Ki-67表达,克隆性能力).
主要成果:
- 在癌细胞中证明了STAT3,PKM2和HIF-1α的构成性激活和相互调节.
- 治疗干预显著降低了STAT3酸化,PKM2核转位和HIF-1α稳定.
- 观察到细胞内ROS降低,乳酸盐产量减少,酸盐增加,转向氧化酸化,Ki-67降低和克隆性能力受损.
结论:
- STAT3-PKM2-HIF-1α/ROS轴是激素独立乳腺癌和前列腺癌中代谢和表型可塑性的关键调节器.
- 这个轴代表了治疗策略的有希望的分子标,旨在调节与癌症相关的代谢表型.
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