Exploration on Potential Action Mechanism of Dendrobii Caulis in Anti-Lung Cancer Therapy Based on Network Pharmacology and Molecular Docking Techniques
Abstract: Objective: To screen the active components and potential targets of Dendrobii Caulis by network pharmacology and molecular docking techniques,and to reveal the action mechanism of Dendrobii Caulis's anti-lung cancer effects. Methods:The BATMAN-TCM database was used to screen the active components of Dendrobii Caulis and their corresponding potential targets. Lung cancer-related genes were screened from the GeneCards, OMIM, PharmGkb,TTD,and DrugBank databases. Venny2.1 was used to obtain the intersection of active component targets and lung cancer targets;Cytoscape 3.7.2 software was used for data visualization to create an active component-targetlung cancer network diagram of Dendrobii Caulis; the String database was used to construct a protein-protein interaction( PPI) network,and Metascape was used for Gene Ontology( GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of potential targets;Vina software was used for molecular docking to determine the minimum free energy and obtain 3D binding models. The UALCAN and Kaplan-Meier Plotter databases were used to analyze the expression of core target genes and the prognosis. Results:A total of 60 potential targets were screened,and 57 common targets were obtained by intersecting with 15 217 lung cancer-related targets. GO functional enrichment analysis showed that the biological processes regulated by Dendrobii Caulis in anti-lung cancer mainly focused on ion transport, signal transduction activation, and calcium ion concentration regulation. KEGG pathway enrichment analysis suggested that Dendrobii Caulis is involved in regulating multiple pathways, including calcium signaling pathway, cAMP signaling pathway, fatty acid metabolism, PPAR signaling pathway, and cancer pathways. Protein interaction analysis identified four core genes: cannabinoid receptor 1 (CNR1), glucocorticoid receptor (NR3C1), tumor necrosis factor (TNF), and prostaglandin-endoperoxide synthase 2 (PTGS2). Molecular docking further verified the binding stability of Dendrobii Caulis's active components (Denbinobin, Dentatin, 24- hydroxy-11-deoxoglycyrrhetinic acid) with these four core genes. CNRL, NR3C1, PTGS2 showed significant differences between lung cancer tissues and tissues adjacent to cancer. Survival analysis indicated that the overall survival (OS) of the high expression groups of CNR1,NR3C1,and PTGS2 was longer than that of the low expression groups. Conclusion: The active components of Dendrobii Caulis may exert their anti-lung cancer effects mainly by regulating the expression levels of cellular cyclins and kinases through acting on CNR1,NR3C1,TNF,and PTGS2 genes,or inhibiting the production and release of inflammatory factors.