Systematic understanding of the underlying target and mechanism of sanguinarine against nasopharyngeal carcinoma through a networkpharmacology approach

Background:Nasopharyngeal carcinoma is a malignant tumor,well known as a cancer type characterized by regional specificity,especially in Southern China.The network pharmacology is an emerging discipline developed in recent years,which has been effectively used to predict the potential therapeutic compounds against disease focusing on the possible therapeutic targets and mechanisms.Sanguinarine,a traditional natural plant-derived phenanthridine alkaloid,has been reported to have a wide variety of pharmacological activities for decades.Methods:In the current study,using the comprehensive network pharmacological method,the potential drug targets of sanguinarine against nasopharyngeal carcinoma were successfully predicted,and verified by molecular docking.The underlying pharmacological mechanism was initially unraveled.Results:Totally,38 potential common targets were confirmed from these potential nasopharyngeal carcinoma therapeutic targets and pharmacological targets of sanguinarine.Their enrichment analyses of GO functions show that protein serine/threonine kinase activity,histone kinase activity,integrin binding,protein tyrosine kinase activity,and cell adhesion molecule binding were top listed.KEGG functional enrichment analysis indicates that the potential pathways are mainly involved into PI3K-Akt signaling pathway.The"drug-target-disease-pathway"network model diagram points out the key genes containing MAPK10,MAPK14,JAK2,BRAF,GSK3B,MET,HSP90AA1,SRC,et al..According to the results of molecular docking,it was further verified that sanguinarine has strong binding ability with MAPK10 and MAPK14.Conclusion:Taken together,this study would provide a clarified theoretical basis for the subsequent wet laboratory research focusing on sanguinarine against nasopharyngeal carcinoma.