NSAID-Au(I) 复合物诱导ROS驱动的DAMP和交叉炎症,以刺激对卵巢癌的免疫反应
Zhongren Xu1, Qiuyue Lu1, Min Shan1
1Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, P. R. China.
Journal of medicinal chemistry
|June 9, 2023
概括
一种新型的黄金I复合物Npx-Au通过诱导氧化应激和免疫反应,对抗卵巢癌具有强烈的抗瘤活性. 这种化合物为结合化疗和免疫治疗提供了一个有希望的策略.
科学领域:
- 药用化学 医学化学
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
背景情况:
- 炎症与卵巢癌的发展有关.
- 抗化学反应在治疗卵巢癌方面是一个重大挑战.
研究的目的:
- 设计和合成由NSAID或类似物衍生的新型黄金 (I) 复合物用于卵巢癌治疗.
- 为了评估最有前途的黄金 (I) 复合物的抗瘤活性和潜在机制,Npx-Au.
主要方法:
- 金的合成 (I) 复合物.
- 在体外评估抗瘤活性和氧化应激诱导.
- 涉及TrxR活性,COX-2和PD-L1表达的机制研究.
- 免疫反应刺激的体内评估,包括DC成熟和T细胞透.
主要成果:
- 与西斯相比,黄金 (I) 复合体B3 (Npx-Au) 显示出更高的抗瘤活性.
- Npx-Au诱导氧化应激和与损伤相关的分子模式 (DAMPs) 通过抑制硫素减少酶 (TrxR) 活性.
- 治疗Npx-Au导致同时降低循环氧化酶-2 (COX-2) 和编程死亡配体1 (PD-L1) 的调节.
- 在体内研究表明,Npx-Au通过减少PD-L1刺激免疫反应,促进树突细胞 (DC) 成熟,并增加CD4+和CD8+T细胞的透.
结论:
- 黄金 (I) 复合体Npx-Au有效地引起免疫细胞死亡 (ICD).
- 通过结合化疗和免疫疗法,Npx-Au显示出作为卵巢癌治疗剂的潜力.
- 这项研究提出了一个有前途的策略,以克服抗化学药性并提高卵巢癌的治疗疗效.
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