摘要
本文通过网络药理学和分子对接技术探讨槐角丸治疗结肠癌(colon cancer,CC)的有效活性成分及作用机制。利用TCMSP数据库检索槐角丸的活性化合物及靶点;OMIM、DisGeNET、GeneCards数据库收集CC的相关靶点、运用STRING数据库和CytoScape软件构建“主要活性成分-靶点”网络以及药物与疾病共同靶点的PPI网络图。利用CytoScape筛选出关键靶点并使用Metascape数据库对其进行GO富集和KEGG通路注释分析,预测其作用机制。利用分子对接技术验证槐角丸与关键靶点之间的关系。最终共选出槐角丸中6种药材对应的230个靶点,其中CC有130个共表达靶点,核心靶点13个。核心靶点共涉及406条GO分析条目及127条KEGG信号通路。预测槐角丸治疗CC的关键活性成分可能为β-谷甾醇、山柰酚和汉黄芩素,过程主要涉及TP53、HSP90AA1、AKT1、MAPK3、MAPK1、RELA等靶点,并通过介导癌症相关通路、PI3K-AKT信号通路、癌症中的蛋白多糖、TNF信号通路、IL-17信号通路等来发挥治疗CC的作用。分子对接显示,β-谷甾醇、山柰酚、汉黄芩素、柚皮素、川陈皮素与TP53、HSP90AA1、AKT1、MAPK3之间具有良好的结合力。生存分析结果显示,HSP90AA1、CAV1、ESR1、MAPK8高表达的患者总生存期显著低于低表达组,TP53、MAPK1、EGFR、RXRA高表达患者的总生存期则显著高于低表达组。本文通过网络药理学研究了槐角丸治疗CC的主要活性成分及其对应的靶点和作用通路,为槐角丸治疗CC提供了新思路。
In this paper,the effective active components and mechanism of Huaijiao pills in the treatment of colon cancer(CC)were discussed by network pharmacology and molecular docking technology.We use TCMSP database to search the active compounds and targets of Huaijiao pills;OMIM,DisGeNET and GeneCards databases to collect the relevant targets of CC,STRING database and CytoScape software to construct the“main active ingredient-target”network and PPI network diagram of the common targets of drugs and diseases.The key targets were screened by CytoScape and analyzed by GO enrichment and KEGG pathway annotation using Metascape database to predict their mechanism.The relationship between Huaijiao pills and key targets was verified by molecular docking technology.230 targets corresponding to 6 kinds of medicinal materials in Huaijiao pills were selected,including 130 co-expression targets and 13 core targets in CC.The core target involves 406 GO analysis items and 127 KEGG signaling pathways.It is predicted that the key active components of Huaijiao pills in the treatment of colon cancer may beβ-sitosterol,kaempferol and wogonin.The process mainly involves TP53,HSP90AA1,AKT1,MAPK3,MAPK1,RELA and other targets,and plays a role in the treatment of colon cancer by mediating cancer-related pathway,PI3K-AKT signaling pathway,proteoglycan in cancer,TNF signaling pathway and IL-17 signaling pathway.Molecular docking showed thatβ-sitosterol,kaempferol,wogonin,naringin and nobiletin had good binding force with TP53,HSP90AA1,AKT1 and MAPK3.Survival analysis showed that the overall survival time of patients with high expression of HSP90AA1,CAV1,ESR1 and MAPK8 was significantly lower than that of patients with low expression,while the overall survival time of patients with high expression of TP53,MAPK1,EGFR and RXRA was significantly higher than that of patients with low expression.In this study,the main active components of Huaijiao pills in treating CC and their corresponding targets and action pathways were studied through netwo
作者
孙凯隆
王泽溢
王毓麟
SUN Kailong;WANG Zeyi;WANG Yulin(Graduate School,Tianjin University of Traditional Chinese Medicine,Tianjin 300110,China;Department of Gastroenterology,Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital,Tianjin 300131,China)
出处
《生命的化学》
CAS
2024年第3期514-526,共13页
Chemistry of Life
基金
天津市救援医学临床医学研究中心资助项目(15ZXLCSY00040)。
关键词
槐角丸
结肠癌
网络药理学
分子对接
Huaijiao pills
colon cancer
network pharmacology
molecular docking
