基于网络药理学和分子对接技术分析白屈菜红碱抗乳腺癌的作用机制

The mechanism of chelerythrine against breast cancer by network pharmacology and molecular docking

目的利用网络药理学和分子对接技术研究白屈菜红碱抗乳腺癌的作用机制。方法通过Swiss Target Pretion数据库预测白屈菜红碱作用的靶点集,Mala Cards数据库收集乳腺癌的相关靶点集,取疾病与药物的靶点交集作为白屈菜红碱抗乳腺癌的潜在作用靶点;应用STRING数据库构建靶点蛋白相互作用网络(PPI),并进行拓扑网络分析得到白屈菜红碱抗乳腺癌的核心靶基因;通过Metascape数据库进行基因本体论功能(GO)和京都基因与基因组百科全书通路(KEGG)富集分析;使用Kaplan-Meier Plotter数据库分析核心靶基因的表达与乳腺癌生存期的相关性;借助AutoDock Vina将核心靶基因与白屈菜红碱进行分子对接。结果通过靶点交集获得白屈菜红碱抗乳腺癌的靶点37个,随后经过拓扑分析得到关键靶点8个;GO富集涉及317个条目;KEGG通路富集分析得到80个条目,主要涉及PI3K/AKT信号通路、VEGF信号通路、ErbB信号通路等;生存期分析结果显示,CHEK1、PIK3CA、mTOR和PTGS2基因的表达量与乳腺癌患者的生存期具有相关性;分子对接结果显示,白屈菜红碱与关键靶点具有较好的结合活性。结论白屈菜红碱可能通过PI3K/AKT信号通路发挥抗乳腺癌的作用,并具有发展成为乳腺癌临床用药的潜力。

Objective To investigate the mechanisms of chelerythrine on the treatment of breast cancer based on network pharmacology and molecular docking.Methods The targets corresponding to chelerythrine and breast cancer were obtained from Mala Cards and Swiss Target Prediction databases.Chelerythrine-related and breast cancer-related targets were found and then combined to get an intersection,which represented potential anti-breast cancer targets of chelerythrine.A protein-protein interaction(PPI)network was constructed from the STRING database and key genes were screened using the topological analysis.Gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis of targets were conducted using metascape database.The relationshipbetween the expressions of key target genes and the survival curve was analyzed using the Kaplan-Meier Plotter database.Molecular docking analysis was performed by AutoDock Vina to verify whether chelerythrine has a definite affinity with key targets.Results A total of 37 potential targets were obtained in chelerythrine against breast cancer.The result of the topology analysis included 8 key targets.The GO enrichment analysis included 317 GO items.The KEGG pathway analysis included 80 pathways,which were closely related to the PI3K/AKT signaling pathway,the ErbB signaling pathway,VEGF signaling pathway,and others.The results of the survival curve analysis showed that the expression levels of CHEK1,PIK3CA,mTOR and PTGS2 genes were related to the survival time of breast cancer patients.The results of molecular docking proved that the combined activity of chelerythrine with key targets was excellent.Conclusion Chelerythrine may play an anti-breast cancer role via the PI3K/AKT signaling pathway and has the potential to be developed into a clinical drug for breast cancer.