Exploring the mechanism of platycodin D in inhibiting nasopharyngeal carcinoma based on network pharmacology combined with experimental validation

Objective To delve into the underlying mechanism of platycodin D in inhibiting nasopharyngeal carcinoma (NPC) through a combination of network pharmacology and cellular experimental techniques.

Methods The corresponding targets of platycodin D and nasopharyngeal carcinoma were obtained from Pubchem, PharmMapper, and GeneCards databases, and their intersection was input into the DAVID database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network of the intersection targets and the"platycodin D-target-nasopharyngeal carcinoma-pathway" network model were obtained using the STRING database and Cytoscape software. Relevant signaling pathways and core targets were screened and obtained, and molecular docking was performed between the top five core targets and platycodin D. Cell counting kit-8 (CCK-8) assay, plate cloning experiment, wound healing experiment, and Calcein-AM/PI staining were used to evaluate the effects of platycodin D on the proliferation, colony formation, migration and apoptosis of nasopharyngeal carcinoma cells. Western blotting was employed to verify the expression levels of proteins related to the MAPK/ERK pathway.

Results Network pharmacology analysis identified 115 potential therapeutic targets. GO and KEGG enrichment analyses yielded 309 biological processes, 44 cellular components, 83 molecular functions, and 125 signaling pathways. By integrating PPI, drug-target-diseasepathway network models and KEGG enrichment results, 10 core targets including MAPK1, HRAS, GRB2, MAPK8, and MAPK10 were identified, with MAPK1 having the highest degree value. The molecular docking results showed that platycodon D had good binding activity with the core target. Cellular experiments revealed that platycodin D significantly inhibited NPC cell proliferation, migration, and colony formation, while inducing apoptosis and down-regulating the expression of p-ERK protein (P < 0.05).

Conclusion Platycodin D may exert its anti-NPC effects by inhibiting the activation of the MAPK/ERK signaling pathway through down-regulating the expression of p-ERK protein.