基于网络药理学的大黄蛰虫丸治疗结直肠癌作用机制研究

Network pharmacology-based study on the mechanism of action of Dahuang Zhechong pills in the treatment of colorectal cancer

目的:探讨大黄蛰虫丸治疗结直肠癌的药效物质基础以及作用机理。方法:利用TCMSP、TCMID系统并通过文献研究,以获得大黄蛰虫丸的主要化学成份及其功效靶位。再根据GeneCards中的结直肠癌药物靶位、DrugBank中的结直肠癌阳性药功能靶位相结合,证明大黄蛰虫丸功效靶位与结直肠癌之间的相互作用。借助Cytoscape3.7.1软件构建“组分-靶点”网络模型。最后,借助DAVID将主要靶点映射KEGG通路上,进一步阐释主要靶点与大黄蛰虫丸治疗结直肠癌的潜在联系。结果:“组分-靶点”网络包含226个化学组分和相应靶点34个(其中关键药效组分7个,主要靶点26个),主要靶点涉及NOS2、PPARG、PIK3CG、F2、GSK3B、CDK2、PGR、CHEK1等。映射KEGG通路111条(P<0.05),涉及的通路有PI3K-Akt通路、TNF通路、VEGF通路等。结论:结合文献和预测结果分析,榭皮素、L-尿苷为大黄蛰虫丸发挥抗结直肠癌作用的关键药效分子,其机制可能与PI3K-Akt信号通路有关。

Objective:To explore the material basis and mechanism of Dahuang Zhechong pills in the treatment of colorectal cancer.Methods:By using TCMSP,TCMID system and literature research,the main chemical composition and efficacy target of Dahuang Zhechong pill were obtained.According to the colorectal cancer drug targets in GeneCards and the functional targets of colorectal cancer positive drugs in DrugBank,the interaction between the efficacy targets of Dahuang Zhechong pill and colorectal cancer can be proved.Cytoscape3.7.1 software was used to construct the"component-target"network model.Finally,the main targets were mapped to the KEGG pathway with the help of DAVID to further elucidate the potential relationship between the main targets and Dahuang Zhechong pills therapy for colorectal cancer.Results:The"component-target"network consists of 226 components and 34 corresponding targets(including 7 key components and 26 main targets),the main targets include NOS2 PPARG、PIK3CG、F2、GSK3B、CDK2、PGR、CHEK1,etc.There are 111 KEGG mapping signaling pathways(P<0.05),including PI3K-Akt pathway,TNF pathway and VEGF pathway etc.Conclusion:Combined with the literature and forecast result analysis,quercetin and L-uridine are the key components of Dahuang Zhechong pills for treatment of colorectal cancer,and its mechanism is perhaps connected with PI3K-Akt signal pathway.