锡利比宁通过调节瘤免疫微环境在三阴性乳腺癌中的抗癌作用
Shubham D Mishra1, Patricia Mendonca1,2, Sukhmandeep Kaur1
1Division of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Tallahassee, FL 32307, USA.
International journal of molecular sciences
|July 12, 2025
概括
西利比宁通过调节瘤免疫微环境和氧化还原通路,在三阴性乳腺癌 (TNBC) 中克服治疗耐药性的承诺. 这种天然化合物可以逆转免疫抑制,并提高TNBC的化疗效果.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 三重阴性乳腺癌 (TNBC) 由于其侵略性和对常规治疗的耐药性, presents显著的治疗挑战.
- 目前的治疗方法,如化疗和免疫检查点抑制剂,往往对TNBC无效,因为瘤异质性,免疫抑制和改变的氧化还原通路.
研究的目的:
- 探索西利比宁在克服TNBC治疗耐药性的潜力.
- 为了调查silibinin在调节瘤免疫微环境 (TIME) 和氧化还原平衡中的作用机制.
主要方法:
- 在TNBC模型中对西利比宁影响的临床前研究的综述.
- 分析西利比宁对关键信号通路 (JAK/STAT3,NF-κB,Nrf2) 和细胞过程 (EMT,CSCs) 的影响.
- 评估silibinin与免疫细胞的相互作用及其对PD-L1表达的影响.
主要成果:
- 西利比宁抑制PD-L1,NF-κB驱动的炎症,以及与瘤相关的巨细胞招募.
- 它通过Nrf2-EGFR-MYC-TXNIP轴扰乱了氧化还原适应,增强了氧化应激和化学敏感性.
- 西利比宁抑制了表皮-介质细胞过渡,减少了癌症干细胞,并与PD-1 抑制剂协同作用.
结论:
- 西利比宁通过重塑 TIME 和逆转 TNBC 中的化学抵抗,表现出多方面的抗癌作用.
- 它的双重抗氧化和免疫调节特性使其成为TNBC的有前途的辅助疗法.
- 需要先进的配方来克服silibinin的生物可用性限制,以提高临床疗效.
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