IntroductionColorectal 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.MethodsThis 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.ResultsThe 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.DiscussionThis 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.

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牡荆素与阿司匹林联用对结直肠癌的潜在调控机制：基于系统生物学、分子对接、分子动力学模拟和体外研究

简介结直肠癌（CRC）是一种非常流行的消化系统恶性肿瘤。阿司匹林是目前最有前途的CRC化学预防药物之一，阿司匹林与天然化合物的联合有助于增强阿司匹林的抗癌活性。牡荆素等天然黄酮类化合物具有针对结直肠癌的抗癌活性。方法本研究通过网络药理学、分子对接、分子动力学模拟等方法研究牡荆素与阿司匹林的新型组合抗结直肠癌的潜在作用机制。体外结果网络药理学结果表明牡荆素和阿司匹林通过NFKB1、PTGS2（COX-2）、MAPK1、MAPK3和TP53等多种靶蛋白调节多种信号通路。细胞实验表明，牡荆素和阿司匹林的联合作用显着抑制HT-29细胞的生长。牡荆素剂量依赖性地抑制细胞内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。讨论本研究为结直肠癌药物的应用提供了药效学材料和理论依据。耐药性的发展并改善癌症患者的预后。