Molecular mechanism of sophoridine in the treatment of prostate cancer based on cell experiments in vitro and network pharmacology
The effect of Sophoridine(SRI)on the proliferation and apoptosis of DU-145 prostate cancer cells,as well as its mechanism of action were investigated based on cell experiments in vitro,network pharmacology and molecular docking.MTT,colony formation,and immunofluorescence assays were used to detect the effects of SRI on DU-145 cell proliferation,and flow cytometry was used to detect cell apoptosis.qPCR was used to detect the mRNA expression of Ki67,PCNA,Caspase-3/7,Bcl-2,Bax and p38MAPK.The protein expression of PCNA,Caspase-3,Bcl-2,Bax,p38MAPK and p-p38MAPK were detected by Western blot.Several databases,including TCMSP,HERB,Swiss Target Prediction,and PharmMapper were utilized to obtain SRI targets and the OMIM and GeneCards databases were used to collect prostate cancer targets.Common targets between the two datasets were screened using Venny2.1.0.The STRING database was used to construct a protein-protein interaction(PPI)network,and network topology analysis and PPI network visualization were performed using Cytoscape3.9.0 software.GO enrichment and KEGG pathway analysis were performed by DAVID database.Molecular docking was performed using AutoDock l.5.6 software.The results of cell experiments showed that SRI significantly inhibited DU-145 cell proliferation and promoted apoptosis.The PPI network analysis revealed 16 core targets including ALB,MAPK1,CASP3,MAPK8,and p38MAPK.The GO enrichment analysis yielded 158 entries(P＜0.01),were mainly concentrated in apoptosis process,protein phosphorylation,and protein serine/threonine/tyrosine kinase activity.KEGG enrichment analysis obtained 84 signa-ling pathways(P＜0.01),involving cancer pathways,proteoglycans in cancer,MAPK signaling pathway and other signaling pathways.Molecular docking results showed that SRI can stably bind to the core target p38MAPK.qPCR and Western blot re-sults confirmed that SRI can promote the expression of p38MAPK.In conclusion,this study shows that SRI can inhibit the proliferation and promote apoptosis of DU-145 prostate cancer cells,which may be associated with p38MAPK activation.
万方数据
维普
