The mechanism of chelerythrine against breast cancer by network pharmacology and molecular docking / 西安交通大学学报(医学版)

ABSTRACT

【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 relationship between 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.