目的 利用生物信息學(xué)結(jié)合網(wǎng)絡(luò)藥理學(xué)及分子對接系統(tǒng)性探索芹菜素抗前列腺癌的分子機制。方法 通過ETCM、HERB、HIT 2.0及SwissTargetPrediction數(shù)據(jù)庫預(yù)測芹菜素靶點。計算TCGA和GEO數(shù)據(jù)集差異基因作為前列腺癌預(yù)測的疾病靶點，并檢索GeneCards和OMIM數(shù)據(jù)庫作為補充。應(yīng)用STRING數(shù)據(jù)庫和Cytoscape軟件構(gòu)建靶點蛋白相互作用（PPI）網(wǎng)絡(luò)，并篩選核心靶點。采用Metascape數(shù)據(jù)庫進(jìn)行富集分析，使用PyMOL、AutoDock Tools、AutoDock Vina軟件以及PDB數(shù)據(jù)庫進(jìn)行分子對接。結(jié)果 共預(yù)測到236個芹菜素抗前列腺癌作用靶點，主要與激素反應(yīng)、細(xì)胞死亡調(diào)控及激酶調(diào)節(jié)有關(guān)，且京都基因與基因組百科全書（KEGG）富集通路與前列腺癌密切相關(guān)。篩選得到70個核心靶點，分子對接發(fā)現(xiàn)B細(xì)胞淋巴瘤因子-2（Bcl-2）、V-Jun肉瘤病毒癌基因同源物（JUN）、低氧誘導(dǎo)因子-1A（HIF-1A）、腫瘤壞死因子（TNF）、ERG、雌激素相關(guān)受體α（ESRRA）與芹菜素有良好結(jié)合力。結(jié)論 芹菜素通過多靶點和多通路實現(xiàn)抗前列腺癌作用。

Objective To explore the molecular mechanism of apigenin against prostate cancer through bioinformatics combined with network pharmacology including molecular docking. Methods To predicted apigenin drug targets were by ETCM, HERB, HIT 2.0 and SwissTargetPrediction databases. Differential genes in TCGA and GEO data sets were calculated as prostate cancer prediction targets, and supplemented by GeneCards and OMIM databases. STRING database and Cytoscape software were used to construct the target protein interaction network and screen the core targets. Metascape platform was used for target enrichment analysis. Softwares such as PyMOL, AutoDock Tools, AutoDock Vina and PDB database were used for molecular docking. Results A total of 236 apigenin against prostate cancer targets were predicted, mainly related to response to hormone, positive regulation of cell death and regulation of kinase activity, and the KEGG enrichment pathways were closely related to prostate cancer. Among the 236 targets, 70 key targets were identified by molecular docking. Bcl-2, JUN, HIF-1A, TNF, ERG, and ESRRA had a good binding ability with apigenin. Conclusion Apigenin exerts anti-prostate cancer effect through multi-target and multi-pathway mechanisms.

R285

廣東省醫(yī)學(xué)科學(xué)技術(shù)研究基金項目（A2020239）