铁灭症诱导,基生物合成干扰和前列腺癌抑制通过基和维生素D组合的基和维生素D组合
Bobae Park1, Subash Khadka1, Jungmi Ahn1
1Department of Molecular Medicine, University of Texas Health San Antonio,8403 Floyd Curl Drive, San Antonio, TX 78229, USA.
Biochimica et biophysica acta. General subjects
|May 30, 2025
概括
生理维生素D (醇) 与雄激素 (5α-DHT) 结合,通过诱导细胞循环停止和铁亡,抑制了抗割的前列腺癌 (CRPC). 这种组合为晚期前列腺癌的高剂量疗法提供了更安全的替代方案.
科学领域:
- 在瘤学瘤学.
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 激素维生素D (酸) 显示抗癌作用,但在高剂量的毒性临床上受到限制.
- 现有的割抵抗性前列腺癌 (CRPC) 治疗方法通常涉及高剂量的雄激素,并存在安全问题.
研究的目的:
- 为了研究低剂量酸盐与生理水平的雄激素 (5α-dihydrotestosterone,5α-DHT) 结合对CRPC的疗效.
- 探索潜在的分子机制,包括细胞循环调节,雄激素代谢和铁.
主要方法:
- 同时处理CRPC细胞与亚纳米/低纳米酸和生理5α-DHT.
- 细胞循环进展 (G1/S),增殖,迁移,入侵和克隆生长的评估.
- 对关键基因/蛋白质表达 (AKR1D1,HSD3β1,LC3B,GPX4,NCOA4,ALOX-5,PTGS2) 和脂质过氧化的分析.
主要成果:
- 该组合本身没有抑制作用,在体外和体内显著抑制了CRPC细胞.
- 酸/5α-DHT的联合治疗上调调节了安卓基因失活的AKR1D1和下调调节了安卓基因生物合成的HSD3β1,减少了细胞内安卓基因.
- 激素组合诱导的自中介性铁亡 (ferritinophagy),由LC3B诱导,费里丁减少,脂质过氧化和GPX4下调证明.
结论:
- 同时服用生理维生素D和雄激素有效抑制CRPC的进展.
- 该机制涉及细胞循环停止,改变雄激素代谢和铁灭诱导.
- 与高剂量雄激素疗法相比,这种组合代表了晚期前列腺癌的潜在更安全和更有效的治疗策略.
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