| Objective:Prostate cancer(PCa)is one of the common malignant tumors for male,with prostate cancer incidence and mortality increasing year by year.In the advanced stage of disease development,PCa often progresses into castration-resistant prostate cancer(CRPC)accompanied by metastasis.Second-generation androgen receptor inhibitors and chemotherapy drugs are the main drugs for treating castration-resistant prostate cancer.But patients with CRPC tend to develop resistance to these drugs,resulting in a poor prognosis and low survival rate.Therefore,it is urgent to find new and more effective drugs and targets for the treatment of prostate cancer during the onset and progression to castration-resistant prostate cancer.In this study,bioinformatics was used to analyze prostate cancer gene chips to obtain the core genes of prostate cancer development.Molecular docking virtual screening technology and CMap drug relocation technology were applied to explore candidate compounds with therapeutic effects on prostate cancer.Methods:Gene expression profiles of prostate cancer patients were downloaded from the GEO database and TCGA database.R language was used to analyze differentially expressed genes(DEGs)between prostate tumor tissue and normal prostate tissue.Functional enrichment analysis of DEGs was performed using the DAVID database and R language.The protein-protein interaction network(PPI)of DEGs was constructed by the STRING database,and Cytoscape software was applied to screen core genes.The GEPIA database and HPA database were used to verify the core genes.In addition,molecular docking virtual screening technology and CMap drug relocation technology were used to screen the candidate compounds that have therapeutic effects on prostate cancer.Swiss ADME was used to analyze the chemo-chemical properties of the candidate compounds for the treatment of prostate cancer,and the internal structure and properties of the candidate compounds were analyzed by quantum chemical calculation.The effects of candidate compounds on the activity of prostate cancer cells were preliminarily verified by thiazole blue(MTT)colorimetry.Results:1.There were 2067 DEGs between normal and tumor,including 1467 up-regulated genes and 1881 down-regulated genes.GO analysis and KEGG analysis of the DEGs showed that DEGs were mainly concentrated in cell-substrate adhesion,protein binding,actin binding,ECM-receptor interaction,cell cycle,pathways in cancer and cell aging,etc.2.A PPI network of DEGs was constructed,CCNB1,CDK1,TOP2 A,AURKB,CCNB2,RAD51,UBE2 C,AURKA,and KIF11 as core genes were identified by GEPIA and HPA.3.Through molecular docking virtual screening,six small molecular compounds were tightly bound to proteins encoded by multiple core genes,showing therapeutic potential for prostate cancer,namely ZINC25665008,ZINC15228277,ZINC63386413,ZINC78550085,ZINC55370357,and ZINC72135249.4.CMap database was used for drug repositioning,and 233 drugs with potential therapeutic effect on prostate cancer were obtained,including CDK inhibitors,HDAC inhibitors,m TOR inhibitors,topoisomerase inhibitors,and cardiac glycosides,etc.5.Preliminary verification of MTT cell activity showed that cardiac glycosides could inhibit the proliferation of prostate cancer cell line DU145.Conclusion:In this paper,through the bioinformatics analysis of prostate cancer gene chips,nine core genes CCNB1,CDK1,TOP2 A,AURKB,CCNB2,RAD51,UBE2 C,AURKA,and KIF11 were found to play a crucial role in the occurrence and development of prostate cancer.Six compounds with therapeutic potential for prostate cancer were obtained by molecular docking virtual screening.CMap drugs repositioned were to obtain potential drugs for prostate cancer treatment,including CDK inhibitors,HDAC inhibitors,m TOR inhibitors,topoisomerase inhibitors,and cardiac glycosides.Cytological experiments were conducted to verify the primary activity of cardiac glycosides.The results showed that these compounds could effectively inhibit the proliferation of prostate cancer cells. |
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