黑茶的生物活性植物成分重新调整NRF2在肺腺癌癌中的抗癌活性
Suchisnigdha Datta1, Anupam Bishayee2, Dona Sinha1
1Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.
Frontiers in pharmacology
|June 12, 2023
概括
黑茶 (BT) 调节核因素红色素2相关因子2 (NRF2) 途径,增强肺腺癌 (LUAD) 中化疗的有效性. 这种植物化学方法为改善癌症治疗中药物反应提供了一种多模式策略.
科学领域:
- 分子瘤学分子瘤学
- 癌症药理学 癌症药理学
- 植物化学研究 植物化学研究
背景情况:
- 核素红色素2相关因子2 (NRF2) 的构成性激活是癌细胞治疗抵抗的一个关键机制.
- 植物化学物质,包括黑茶 (BT) 中发现的植物化学物质,已经显示出调节NRF2活性的潜力.
- 肺腺癌 (LUAD) 经常表现出NRF2放松调节的化学抵抗,需要新的治疗策略.
研究的目的:
- 调查假设,LUAD中的NRF2放松调节的化学抵抗可以通过富含theaflavin的黑茶 (BT) 抵消.
- 阐明BT介导的NRF2调制机制在不同的LUAD细胞系中,具有不同的NRF2/KEAP1配置.
- 评估BT作为一种多模式剂的潜力,以提高LUAD中的化学敏感性.
主要方法:
- 用BT在不同度和持续时间对LUAD细胞系 (A549和NCI-H23) 的治疗.
- 评估NRF2表达,下游目标以及相关的信号通路 (KEAP1,EGFR,RAS,RAF,ERK,MMP).
- 与药理学NRF2抑制剂 (ML-385) 和激活剂 (三级-丁基) 的比较分析.
主要成果:
- 通过hormetically降低NRF2及其点的调节,BT预处理使A549细胞 (NRF2突变) 对cisplatin敏感.
- BT表现出双向NRF2调节:在A549中低度下调NRF2,而在NCI-H23中高度上调NRF2 (KEAP1过度表达).
- BT影响了KEAP1依赖和KEAP1独立的信号通路,包括EGFR/RAS/RAF/ERK轴.
结论:
- 黑茶 (BT) 显示出一种强大的多模式能力,可以调节LUAD细胞中的NRF2/KEAP1轴.
- 由BT介导的NRF2双向调节可以通过优化NRF2通路活性来提高化疗结果.
- 与合成调节剂相比,BT是改善LUAD药物反应的有希望的天然化合物,可能作为优越的抗癌剂.
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