Han Xinyue, Yang Chao, Guo Cui, Xu Yimin, Liu Xiaoqiang, Xie Runnan, Meng Xiangxue, Cheng Zhihong, Fu Xiaoling
Second Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
Liaoning University of Traditional Chinese Medicine, Shenyang 100021, Liaoning, China.
Evid Based Complement Alternat Med. 2021 Nov 12;2021:9132608. doi: 10.1155/2021/9132608. eCollection 2021.
Curcumin is a potential drug for the treatment of colorectal cancer (CRC). Its mechanism of action has not been elucidated. This study aims to investigate the mechanism of action of curcumin in the treatment of CRC via bioinformatics methods such as network pharmacology and molecular docking.
The targets of curcumin and CRC were obtained from the public databases. The component-targets network of curcumin in the treatment of CRC was constructed by Cytoscape v3.7.2. Through protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), important targets and signaling pathways related to CRC treatment were identified. Finally, the results were verified by molecular docking, and the correlation between the key targets and tumor-infiltrating immune cells (TICs) was analyzed.
A total of 30 potential targets of curcumin for CRC treatment were collected. The GO function enrichment analysis showed 140 items, and the KEGG pathway enrichment analysis showed 61 signaling pathways related to the regulation of protein kinase activity, negative regulation of apoptosis process, cancer signaling pathway, and PI3K-Akt signaling pathway. The molecular docking results showed that curcumin could be combined with AKT1, EGFR, and STAT3 more stably, and AKT1 has the strongest binding to curcumin. Bioinformatics analysis discovered that the expression of core targets AKT1, EGFR, and STAT3 in CRC was related to TICs.
This study explored the targets and pathways of curcumin in the treatment of CRC. The core targets are AKT1, EGFR, and STAT3. The study indicated that curcumin has preventive and treatment effects on CRC through multitarget and multipathway, which laid the foundation for follow-up research.
姜黄素是一种治疗结直肠癌(CRC)的潜在药物。其作用机制尚未阐明。本研究旨在通过网络药理学和分子对接等生物信息学方法,研究姜黄素治疗CRC的作用机制。
从公共数据库中获取姜黄素和CRC的靶点。利用Cytoscape v3.7.2构建姜黄素治疗CRC的成分-靶点网络。通过蛋白质-蛋白质相互作用(PPI)、基因本体论(GO)和京都基因与基因组百科全书(KEGG),确定与CRC治疗相关的重要靶点和信号通路。最后,通过分子对接验证结果,并分析关键靶点与肿瘤浸润免疫细胞(TICs)之间的相关性。
共收集到30个姜黄素治疗CRC的潜在靶点。GO功能富集分析显示140项,KEGG通路富集分析显示61条与蛋白激酶活性调节(regulation of protein kinase activity)、凋亡过程的负调节(negative regulation of apoptosis process)、癌症信号通路(cancer signaling pathway)和PI3K-Akt信号通路相关的信号通路。分子对接结果表明,姜黄素与AKT1、EGFR和STAT3的结合更稳定,且AKT1与姜黄素的结合最强。生物信息学分析发现,CRC中核心靶点AKT1、EGFR和STAT3的表达与TICs相关。
本研究探索了姜黄素治疗CRC的靶点和通路。核心靶点为AKT1、EGFR和STAT3。研究表明,姜黄素通过多靶点、多途径对CRC具有预防和治疗作用,为后续研究奠定了基础。