Effect Of Brusatol On Lung Adenocarcinoma And Its Mechanism Based On Network Pharmacology Analysis

Objective Brusatol is a single body extracted from the ripe fruit of the traditional Chinese medicine plant Brucea javanica,and more and more studies have shown that Brusatol has an anti-cancer effect on a variety of tumors.However,the effect and mechanism of Brusatol on lung adenocarcinoma are still unclear,so this paper explores the mechanism of action of Brusatol on lung adenocarcinoma through network pharmacology and a series of basic experimental methods,and strives to provide strong theoretical support for the anti-tumor effect of Brusatol.Methods Drug targets for Brusatol were obtained using the Pharm Mapper online database.The online database TCGA database and R software were used to analyze the differential genes of lung adenocarcinoma,and further screen out the intersection genes of drugs and diseases.Go and KEGG enrichment analysis of intersection targets using R software.Protein network interaction(PPI)was constructed through string database,and the protein regulatory network of Brusatol-lung adenocarcinoma-target was visualized with the help of Cytoscape,and the node degrees of freedom were calculated to screen key genes.Query the genetic variation of core genes in lung adenocarcinoma with the help of the c Bio Portal online database.View immunohistochemical expression of core genes with the help of the Human Protein Atlas Database Library(HPA).The expression of m RNA of core genes in lung adenocarcinoma tumor tissues and normal tissues was analyzed using the GEPIA online database.Molecular docking was used to further screen the tight target bound to Brusatol,and took it as the target gene,the pharmacological effect of Brusatol on lung adenocarcinoma was analyzed by MTT method,colony formation experiments confirmed that Brusatol inhibited the proliferation of lung adenocarcinoma,the effect of Brusatol on proteins in the relevant pathways of lung adenocarcinoma was detected by Western Blot,and the effect of Brusatol on the invasion of lung adenocarcinoma was detected by transwell method.Results By network pharmacological methods,383 corresponding targets of Brusatol,23105 targets of lung adenocarcinoma,and 328 intersection targets were screened.The results of GO enrichment analysis show that the intersecting genes of cholesin-lung adenocarcinoma are mainly involved in the biological behaviors of endopeptidase activity,protein tyrosine kinase activity,steroid homone receptor activity,coenzyme binding,carboxylic and binding,organic acid binding and so on.The enrichment analysis of KEGG pathway found that the progression of lung adenocarcinoma was mainly regulated by Ras signaling pathway,Apoptosis signaling pathway,T cell receptor signaling pathway,VEGF signaling pathway,and PPAR signaling pathway.ALB,SRC,HSP90AA1,HRAS,CASP3,MAPK1,ESR1 may be key targets for the treatment of pulmonary adenocarcinoma.Molecular docking results show that Brusatol directly acts on the MAPK1 target gene,and compared with other target genes,the binding force of Brusatol and MAPK1 is the strongest.It was further demonstrated through molecular biology experiments that Brusatol inhibited the proliferation and migration of lung adenocarcinoma cells,inducing apoptosis and cycle arrest of lung adenocarcinoma cells.With the increase of the dosage of Brusatol and the extension of the action time,the amount of MAPK1 protein expression decreases,and the key protein P-MEK1/2 and p-raf protein expression of RAS signaling channels decreases.Conclusions Alb,SRC,HSP90AA1,HRAS,CASP3,MAPK1,ESR1 as key genes for the treatment of lung adenocarcinoma as Brusatol.The molecular mechanism of Brusatol in the treatment of lung adenocarcinoma is that it targeted MAPK1 to regulate Ras signaling pathway and exerted anti-tumor effect.This study reveals the mechanism of action of Brusatol in the treatment of lung adenocarcinoma,and provides a new idea for the development of Brusatol as an anti-tumor small molecule drug.