Zhou Yulv, Lin Shengnan, Zhong Xinzhu, Huang Fang, Huang Jinxiang, Xu Luning
Department of Chinese Medicine and Anorectology, Sanming First Hospital, Affiliated Hospital of Fujian Medical University, Sanming City, Fujian Province, China.
Department of Clinical Pharmacy, Sanming First Hospital, Affiliated Hospital of Fujian Medical University, Sanming City, Fujian Province, China.
Cell Death Discov. 2024 Dec 18;10(1):504. doi: 10.1038/s41420-024-02223-9.
Among the common malignancies, colorectal cancer (CRC) is often resistant to chemotherapy because of drug resistance and severe toxicity. Currently, aspirin is one of the most promising CRC chemopreventive drugs, both for primary prevention and for reducing the chance of recurrence and metastasis following radical surgery in patients with early-stage CRC. Oleanolic acid is a potential antineoplastic drug that has an antagonistic effect on many kinds of tumors. Network pharmacology, molecular docking, and in vitro experiments were performed to investigate whether OA combined with aspirin can enhance the anticancer effects of aspirin. As indicated by the network pharmacology results, oleanolic acid and aspirin can regulate multiple signaling pathways through multiple target proteins, including NFκB1\IκBα\PTGS2\MAPK3\PIK3CA. A series of cellular experiments demonstrated for the first time that oleanolic acid synergistically enhances aspirin to inhibit the proliferation and invasion of HCT116 and HT29 cells and induce S-phase arrest by regulating Akt/NFκB/IκBα/COX2 signaling pathway, thus synergistically enhancing the ability of aspirin to promote apoptosis of colorectal cancer cells. This study provides a novel approach to the use of fresh medications for the treatment of colorectal cancer and offers a theoretical foundation for the potential creation of aspirin derivatives based on oleanolic acid.
在常见的恶性肿瘤中，结直肠癌（CRC）由于耐药性和严重毒性，往往对化疗耐药。目前，阿司匹林是最有前景的结直肠癌化学预防药物之一，可用于一级预防以及降低早期结直肠癌患者根治性手术后复发和转移的几率。齐墩果酸是一种潜在的抗肿瘤药物，对多种肿瘤具有拮抗作用。本研究通过网络药理学、分子对接和体外实验，探究齐墩果酸（OA）联合阿司匹林是否能增强阿司匹林的抗癌效果。网络药理学结果表明，齐墩果酸和阿司匹林可通过多种靶蛋白调控多条信号通路，包括NFκB1\IκBα\PTGS2\MAPK3\PIK3CA。一系列细胞实验首次证明，齐墩果酸协同增强阿司匹林抑制HCT116和HT29细胞增殖和侵袭的能力，并通过调节Akt/NFκB/IκBα/COX2信号通路诱导S期阻滞，从而协同增强阿司匹林促进结直肠癌细胞凋亡的能力。本研究为结直肠癌的新药应用提供了一种新方法，并为基于齐墩果酸的阿司匹林衍生物的潜在开发提供了理论基础。
