高剂量的维生素C通过激活大肠直肠癌中的AMPK来抑制PD-L1表达
Jia Huang1, Su Min1, Ruiyang Hong1
1Department of Anesthesiology, Technology Innovation Research Center, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Immunobiology
|March 26, 2025
概括
高剂量的维生素C (VitC) 通过抑制华堡效应和降低PD-L1表达的调节来抑制结直肠癌的生长. 这增强了抗瘤免疫力,有望改善癌症免疫疗法.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 生物化学 生物化学
背景情况:
- 结肠直肠癌 (CRC) 免疫疗法,特别是抗PD-1/PD-L1的免疫疗法,显示出有前途但有局限性.
- 维生素C (VitC) 可能在癌症治疗中发挥作用,但其对瘤免疫力的影响尚未完全理解.
- 以前的研究表明,VitC通过抑制华堡效应来抑制瘤生长.
研究的目的:
- 研究高剂量维生素C对结直肠癌中PD-L1表达的作用.
- 阐明VitC影响PD-L1表达和瘤免疫力的潜在机制.
- 评估VitC在增强CRC免疫疗法疗效方面的潜力.
主要方法:
- 评估了VitC对HCT116结直肠癌细胞中有氧糖解和PD-L1表达的影响.
- 研究了AMPK激活在调解VitC对PD-L1.1影响中的作用.
- 研究了VitC对HK2和NF-κB信号通路的影响.
- 对比了单独和组合使用的VitC和阿特佐利祖马布 (抗PD-L1) 的疗效.
主要成果:
- 维生素C抑制了有氧糖解,并在HCT116细胞中降低了PD-L1的表达.
- VitC激活AMPK,导致减少HK2和NF-κB的表达,这反过来又降低了PD-L1水平.
- 维特基因降低PD-L1的调节导致T细胞透率增加.
- VitC和阿特索利祖马布表现出可比的瘤抑制作用,组合疗法显示出增强的疗效.
结论:
- 高剂量的维生素C激活AMPK,降低PD-L1表达的调节,并减轻结直肠癌中的免疫逃避.
- 在CRC中,VitC显示出作为辅助疗法的潜力,以提高PD-L1向免疫治疗在CRC中的疗效.
- 这项研究为优化结直肠癌患者免疫治疗结果提供了一个有希望的策略.
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