Mechanism and Validation of Synergistic Compatibility of "Fuling(Poria)-Gancao(Glycyrrhizae Radix Et Rhizoma)" on Lung Adenocarcinoma Based on Integrated Pharmacology
Objective:To investigate the mechanism and targets of synergistic compatibility of"Fuling(Poria)-Gancao(Glycyrrhizae Radix Et Rhizoma)"on lung adenocarcinoma based on network pharmacology and bioinformatics,and to verify the inhibitory effect of quercetin,the main ingredient of"Fuling-Gancao",on lung adenocarcinoma through experiments.Methods:Differential analysis of lung adenocarcinoma related genes was performed.The active ingredients and targets of"Fuling-Gancao"was downloaded from TCMSP database.And the drug-disease common targets were obtained for network construction,enrichment analysis and survival analysis.Through molecular docking between the main ingredients of"Fuling-Gancao"and the key targets of lung adenocarcinoma,the effective ingredients with good structure-activity relationship were selected for subsequent experimental validation.The intervention effects of the drugs on lung adenocarcinoma cells were detected by cell proliferation,scratch and invasion assays,and the effects of the drugs on key targets were detected by real-time fluorescence quantitative.Results:A total of 32 common genes were obtained by taking the intersection of 8 109 differentially expressed genes and 102 drug target genes in lung adenocarcinoma.Enrichment analysis showed that the target genes were mainly involved in p53 signaling pathway,cellular senescence,and other cancer-related pathways.And the results of molecular docking showed that quercetin had a good structure-activity relationship.Therefore,quercetin was selected for subsequent experimental verification.The active ingredient quercetin can inhibit the proliferation,migration and invasion ability of lung adenocarcinoma A549 and H1299 cells,and can significantly down-regulate the expression of the key targets BIRC5,CCNB1 and CHEK1.Conclusions:Quercetin,the active ingredient of"Fuling-Gancao",can effectively inhibit the malignant phenotype of lung adenocarcinoma.Its mechanism may be related to the targeted regulation of the expression of key genes BIRC5,CCNB1 and CHEK1.
Fuling(Poria)Gancao(Glycyrrhizae Radix Et Rhizoma)quercetinnetwork pharmacologybioinfor-maticslung adenocarcinoma