Molecular docking and big-data bioinformatics predict the mechanisms of action of the active ingredients of Ganoderma lucidum in treating lung cancer

摘要

This study pioneers a network pharmacology-based approach and in silico molecular docking andvisualization approaches to predict the potential molecular mechanisms involved in treatment of lung cancer withLingzhi (Ganoderma lucidum). Methods: The active ingredients of Ganoderma lucidum were screened in theTraditional Chinese Medicine Systems Pharmacology database, and corresponding potential targets of these activeingredients were queried. Then potential targets for the treatment of lung cancer were separately queried using theGeneCards database. The overlapping targets of the active ingredients and lung cancer treatment were furtheranalyzed in silico by calculating degree values and conducting literature searches. A protein-protein interactionnetwork was constructed for these overlapping targets using the STRING database, and a “drug-ingredient-target”network was created using Cytoscape 3.7.1 software. Gene ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed for key targets using Metascape. Finally, the key molecules wereexamined using molecular docking in Autodock 3.7 software, and the representative docking results were visualizedusing PyMol software. Results: A total of 14 active ingredients were identified, including 3 key ingredients(ganolucidic acid E, ergosta-4,6,8(14),22-tetraene-3-one, and beta-sitosterol) and 8 key targets. Gene ontologyanalysis and KEGG enrichment showed that Ganoderma lucidum may act on 10 key signaling pathways, such as theneuroactive ligand-receptor interaction pathway, calcium signaling pathway, and cyclic adenosine monophosphatesignaling pathway, to regulate neuroactivity, ion homeostasis, and other processes, thus inhibiting the progression oflung cancer. Molecular docking results predicted that among the 8 key targets, mu-type opioid receptor, transforminggrowth factor beta-1 proprotein, and apoptosis regulator BAX exhibit better docking with these ligands. Conclusion:The preliminary results of this study identified potential active ingredients of Ganoderma lucidum for the treatmentof lung cancer, and putative mechanisms of action, which could provide a theoretical basis for further experimentalstudies on anticancer efficacy.