Combining network pharmacology and experimental validation to study the action and mechanism of brusatol against lung adenocarcinoma.

Brusatol is a natural product found in the plant Brucea javanica that is used to treat diseases such as amoebiasis and malaria. It also has significant anti-tumor effects. However, its role in lung cancer and the mechanism underlying its pharmacological effects remain unclear. In this study, we identified the core target of brusatol for lung adenocarcinoma (LUAD) therapy using network pharmacology and elucidated its therapeutic mechanism by conducting cell experiments. The therapeutic targets of brusatol were obtained from the PharmMapper database, the LUAD-related genes were obtained from the TCGA database, and the intersection targets of the two were taken as potential targets for treating LUAD with brusatol. Based on the results of the intersection, core target and signaling pathways were identified by protein-protein interaction (PPI), molecular docking, gene ontology (GO) function, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Finally, cell experiments were performed to determine the antineoplastic effect of brusatol on LUAD. We identified 328 potential targets of brusatol for treating LUAD, and the PPI network analysis identified ALB, SRC, HSP90AA1, HRAS, CASP3, MAPK1, and ESR1 as key genes. Through molecular docking, MAPK1 was identified as the core target of brusatol in LUAD. GO analysis revealed that brusatol may exert anti-tumor effects through endopeptidase activity, protein tyrosine kinase activity, and amide binding. KEGG enrichment analysis suggested that brusatol may treat LUAD by regulating the RAS signaling pathway. Brusatol inhibited the proliferation and invasion of LUAD cells and caused apoptosis and G2/M phase arrest in these cells. Further analysis confirmed that brusatol plays a role in treating LUAD by targeting MAPK1 and regulating the Ras signaling pathway. To summarize, through a combination of network pharmacological analysis and cell experimental validation, we revealed the mechanism underlying the therapeutic effects of brusatol on LUAD. This study also provided a theoretical basis for using brusatol as a candidate drug for the targeted therapy of LUAD.