Brucea Javanica Oil Emulsion Injection (BJOEI) has been proven to have extensive anti-tumor effects. But the anti-cancer mechanisms need further exploration. So, the aim of this study was to investigate the role and mechanisms of BJOEI on pancreatic cancer using network pharmacology and experimental validation. Disease targets were obtained from the GSE101448 dataset in the Gene Expression Omnibus (GEO) database. Eight active ingredients were identified following a comprehensive literature search. The target genes of BJOEI were obtained from the SwissTarget Prediction database. The core targets of BJOEI and the involved signaling pathways were determined using the compound-target network, protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. GO and KEGG enrichment analyses of 50 potential overlapping genes indicated that BJOEI exerted therapeutic effects on pancreatic cancer through the apoptotic pathway. In vitro experiments further revealed that BJOEI could suppress cell growth and invasion, arrest cells at the S stage, and cause cell apoptosis in three pancreatic cell lines. Additionally, BJOEI inhibited tumor growth in vivo. Among the 15 key genes regulating apoptosis, 11 were upregulated, while 4 were downregulated. PPARG emerged as a core target in bioinformatics analysis. The ability of PPARG to regulate apoptosis was validated by Western Blot. Our findings verified that BJOEI could regulate apoptosis-related genes, especially PPARG, thereby inducing apoptosis and inhibiting proliferation in pancreatic cancer cells. BJOEI can impede pancreatic cancer progression and induce cell apoptosis. The underlying mechanism appears to be closely associated with the regulation of apoptosis-related genes.
Keywords: Brucea Javanica Oil Emulsion Injection; PPARG; Pancreatic cancer; apoptosis; network pharmacology.
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