Yong Chuan Hospital of Chongqing Medical University, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, People's Republic of China.
College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, Chongqing, People's Republic of China.
Drug Des Devel Ther. 2021 Feb 24;15:705-720. doi: 10.2147/DDDT.S293046. eCollection 2021.
This study aimed to reveal Danggui Buxue Decoction (DBD) candidate targets and mechanisms in the treatment of metastatic colon cancer (MCC), using network pharmacology-based analyses and experimental validation.
Traditional Chinese Medicine Systems Pharmacology (TCMSP) database query and text mining were used to screen active compounds in DBD, and the Swiss target prediction platform was applied to predict compound-related target proteins. Targets likely associated with MCC were determined using GeneCards and OMIM databases. Targets common to DBD and MCC were obtained from the Venn platform; subsequently, Cytoscape was used to construct drug-compound-target-disease and protein-protein interaction networks. The hub gene was determined by R, while GO and KEGG enrichment analyses were performed on common targets to elucidate biological processes and signaling pathways involved in DBD against MCC. Finally, the metastatic colon cancer mouse model was used to detect the levels of expression of protein Bax, Bcl2, Caspase3, and Cleaved caspase3 by Western blot.
A total of 28 active compounds and 61 common targets were predicted. The main compounds were quercetin, hederagenin, jaranol, methylnissolin, formononetin, calycosin, kaempferol, 3.9-di-O-methylnissolin, 24-propylcholesterol, and 7-O-methylisomucronulatol, present in Astragalus membranaceus (Huangqi, HQ). In addition, beta-sitosterol, ferulic acid, and stigmasterol, present in Angelica sinensis (Danggui, DG), were detected. JUN, PTSG2, EGFR, ESR1and, CASP3 genes were the top 5 hub genes in the PPI network. GO and KEGG enrichment analyses indicated that apoptosis played a major role in the biological processes and signaling pathways involved. Moreover, the in vivo experiment revealed that DBD inhibited MCC by up-regulating the expression of Bax, Caspase3, and Cleaved caspase3, and by down-regulating the expression of Bcl2.
This study revealed candidate DBD targets and mechanisms in the treatment of MCC, using network pharmacology-based analyses and experimental validation. The present findings provide a reference for tumor treatment during the perioperative period.
本研究旨在通过网络药理学分析和实验验证，揭示当归补血汤（DBD）治疗转移性结肠癌（MCC）的候选靶点和机制。
利用中药系统药理学（TCMSP）数据库查询和文本挖掘筛选 DBD 中的活性化合物，并利用瑞士目标预测平台预测化合物相关的靶蛋白。利用 GeneCards 和 OMIM 数据库确定与 MCC 相关的靶标。从 Venn 平台获取 DBD 和 MCC 的共同靶标；随后，利用 Cytoscape 构建药物-化合物-靶标-疾病和蛋白质-蛋白质相互作用网络。利用 R 确定枢纽基因，对共同靶标进行 GO 和 KEGG 富集分析，阐明 DBD 治疗 MCC 涉及的生物学过程和信号通路。最后，利用转移性结肠癌小鼠模型通过 Western blot 检测 Bax、Bcl2、Caspase3 和 Cleaved caspase3 蛋白的表达水平。
共预测到 28 种活性化合物和 61 个共同靶标。主要化合物有槲皮素、栀子苷、京尼平苷酸、甲基毛蕊异黄酮、芒柄花苷、大豆苷、山奈酚、3.9-二-O-甲基毛蕊异黄酮、24-丙基胆甾醇、7-O-甲基异牡荆素，均来自黄芪（HQ）。此外，还检测到当归（DG）中的β-谷甾醇、阿魏酸和豆甾醇。PPI 网络中的前 5 个枢纽基因是 JUN、PTSG2、EGFR、ESR1 和 CASP3。GO 和 KEGG 富集分析表明，细胞凋亡在参与的生物学过程和信号通路中起着重要作用。此外，体内实验表明，DBD 通过上调 Bax、Caspase3 和 Cleaved caspase3 的表达，下调 Bcl2 的表达，抑制 MCC。
本研究通过网络药理学分析和实验验证，揭示了 DBD 治疗 MCC 的候选靶点和机制。本研究结果为围手术期肿瘤治疗提供了参考。
