基于网络药理学和分子对接探索L.用于结肠癌治疗的成分及机制。
Exploring the components and mechanism of L. for colon cancer treatment based on network pharmacology and molecular docking.
作者信息
Chen Jin-Fang, Wu Shi-Wei, Shi Zi-Man, Qu Yan-Jie, Ding Min-Rui, Hu Bing
机构信息
Institute of Traditional Chinese Medicine in Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
出版信息
Front Oncol. 2023 Mar 8;13:1111799. doi: 10.3389/fonc.2023.1111799. eCollection 2023.
BACKGROUND
L. (SNL) (Longkui) is a Chinese herb that can be used to treat colon cancer. The present study explored the components and mechanisms of SNL in treating colon cancer by using network pharmacology and molecular docking.
METHODS
The components of SNL were collected from the TCMSP, ETCM, HERB, and NPASS databases. Meanwhile, the target proteins of these ingredients were collected/predicted by the TCMSP, SEA, SwissTargetPrediction, and the STITCH databases colon cancer-related target genes were identified from TCGA and GTEx databases. The interaction networks were established Cytoscape 3.7.2. Gene Ontology and KEGG pathways were enriched by using the David 6.8 online tool. Finally, the binding of key components and targets was verified by molecular docking, and the cellular thermal shift assay (CETSA) was used to detect the efficiency of apigenin and kaempferol binding to the AURKB protein in CT26 cells.
RESULTS
A total of 37 SNL components, 796 SNL targets, 5,356 colon cancer genes, and 241 shared targets of SNL and colon cancer were identified. A total of 43 key targets were obtained through topology analysis. These key targets are involved in multiple biological processes, such as signal transduction and response to drug and protein phosphorylation. At the same time, 104 signaling pathways, such as pathways in cancer, human cytomegalovirus infection, and PI3K-Akt signaling pathway, are also involved. The binding of the four key components (i.e., quercetin, apigenin, kaempferol, and luteolin) and the key targets was verified by molecular docking. The CETSA results showed that apigenin and kaempferol were able to bind to the AURKB protein to exert anti-CRC effects.
CONCLUSIONS
Quercetin, apigenin, kaempferol, and luteolin are the main components of SNL in treating colon cancer. SNL regulates multiple bioprocesses signaling pathways, such as pathways in cancer, PI3K-Akt, and cell cycle signaling pathways.
背景
龙葵是一种可用于治疗结肠癌的中草药。本研究运用网络药理学和分子对接技术，探究龙葵治疗结肠癌的成分及作用机制。
方法
从中药系统药理学数据库与分析平台（TCMSP）、中药综合数据库（ETCM）、草药数据库（HERB）和天然产物活性成分与药物靶点数据库（NPASS）收集龙葵的成分。同时，通过TCMSP、SEA、瑞士靶点预测数据库（SwissTargetPrediction）和STITCH数据库收集/预测这些成分的靶蛋白，并从癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）数据库中鉴定结肠癌相关靶基因。使用Cytoscape 3.7.2软件构建相互作用网络。利用David 6.8在线工具对基因本体（Gene Ontology）和京都基因与基因组百科全书（KEGG）通路进行富集分析。最后，通过分子对接验证关键成分与靶点的结合，并采用细胞热位移分析（CETSA）检测芹菜素和山奈酚在CT26细胞中与极光激酶B（AURKB）蛋白的结合效率。
结果
共鉴定出37种龙葵成分、796个龙葵靶点、5356个结肠癌基因以及241个龙葵与结肠癌的共同靶点。通过拓扑分析获得43个关键靶点。这些关键靶点参与多种生物学过程，如信号转导、药物反应和蛋白质磷酸化。同时，还涉及104条信号通路，如癌症通路、人巨细胞病毒感染通路和PI3K-Akt信号通路。通过分子对接验证了四种关键成分（即槲皮素、芹菜素、山奈酚和木犀草素）与关键靶点的结合。CETSA结果表明，芹菜素和山奈酚能够与AURKB蛋白结合，发挥抗结直肠癌的作用。
结论
槲皮素、芹菜素、山奈酚和木犀草素是龙葵治疗结肠癌的主要成分。龙葵调节多种生物学过程和信号通路，如癌症通路、PI3K-Akt和细胞周期信号通路。
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