Network Pharmacology and Experimental Validation-based Investigation of the Underlying Mechanism of Yi-Yi-Fu-Zi-Bai-Jiang-San of Nasopharyngeal Carcinoma

Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) is a representative traditional Chinese medicine (TCM) formula. However, its potential anti-tumor effects in nasopharyngeal carcinoma (NPC) remains unclear. This study aims to investigate the monomers of YYFZBJS and their associated targets in the treatment of NPC. The primary active compounds of YYFZBJS and their corresponding targets were identified using the TCMSP, SEA, and Super-PRED databases. NPC-related target proteins were retrieved from OMIM, GeneCards, and TTD databases. A protein-protein interaction network was constructed using the common target proteins of YYFZBJS active compounds and NPC. Core genes were identified through three algorithms in CentiScape 2.2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were then performed on these core genes. Validation was conducted using the GSE53819 and GSE13597 datasets. Finally, interactions between core targets and active ingredients were confirmed through molecular docking, molecular dynamics simulations, and cell-based experiments. A total of 715 corresponding to YYFZBJS active compounds and 3159 NPC-related targets were screened. Among these, 143 intersection genes were identified, from which 32 core genes were selected based on degree centrality, closeness centrality, and betweenness centrality. GO and KEGG analyses of these core genes revealed relevant biological processes and pathways. Furthermore, these 32 core genes were cross-referenced with the GSE53819 and GSE13597 datasets, identifying PTGS2 and CCND1 as valid targets of active compounds. Molecular docking, molecular dynamics simulations and cell experiments confirmed the effectiveness of the Acacetin-PTGS2 pathway. Acacetin of the main active ingredient in YYFZBJS suppressed NPC by downregulating PTGS2 expression.