结直肠癌（CRC）是一种高发的消化系统恶性肿瘤。目前，阿司匹林是最有前途的CRC化学预防剂之一，而阿司匹林与天然化合物的联合使用有助于增强阿司匹林的抗癌活性。天然黄酮类物质如槲皮素具有针对结直肠癌的抗癌活性。本研究通过网络药理学、分子对接、分子动力学模拟和体外实验，调查了槲皮素和阿司匹林对结直肠癌的潜在作用机制。网络药理学的结果显示，槲皮素和阿司匹林通过多个靶蛋白（如NFKB1、PTGS2（COX-2）、MAPK1、MAPK3和TP53）调节多条信号通路。细胞实验证实，槲皮素和阿司匹林的联合作用显著抑制了HT-29细胞的生长。槲皮素在细胞中以剂量依赖的方式抑制COX-2的表达，并增强阿司匹林对结直肠癌细胞中COX-2和NF-κB表达的下调。该研究为应用抗结直肠癌剂延缓药物耐药的发展和改善癌症患者的预后提供了药效学材料和理论基础。版权所有 © 2023 Chen、Chen、Huang、Zhang、Zhou和Xu。

Colorectal cancer (CRC) is a highly prevalent digestive system malignancy. Aspirin is currently one of the most promising chemopreventive agents for CRC, and the combination of aspirin and natural compounds helps to enhance the anticancer activity of aspirin. Natural flavonoids like vitexin have an anticancer activity focusing on colorectal carcinoma.This study investigated the potential mechanism of action of the novel combination of vitexin and aspirin against colorectal cancer through network pharmacology, molecular docking, molecular dynamics simulation, and in vitro experiments.The results of network pharmacology suggested that vitexin and aspirin regulate multiple signaling pathways through various target proteins such as NFKB1, PTGS2 (COX-2), MAPK1, MAPK3, and TP53. Cellular experiments revealed that the combined effect of vitexin and aspirin significantly inhibited HT-29 cell growth. Vitexin dose-dependently inhibited COX-2 expression in cells and enhanced the down-regulation of COX-2 and NF-κB expression in colorectal cancer cells by aspirin.This study provides a pharmacodynamic material and theoretical basis for applying agents against colorectal cancer to delay the development of drug resistance and improve the prognosis of cancer patients.Copyright © 2023 Chen, Chen, Huang, Zhang, Zhou and Xu.