目的 基于網絡藥理學和分子對接技術探究白藜蘆醇治療前列腺癌的潛在作用機制。方法 通過TCMSP、HERB、Drugbank等9個藥物靶點數據庫檢索并收集白藜蘆醇的作用靶點；利用DisGeNET、GeneCards、OMIM等6個疾病靶點數據庫獲得前列腺癌的相應靶點；利用Venny 2.1.0平臺獲得藥物和疾病的交集靶點，然后利用String數據庫和Cytoscape 3.9.1軟件的Centiscape 2.2插件進行拓撲分析，進一步篩選得到白藜蘆醇抗前列腺的作用靶點；再次利用String數據庫和Cytoscape 3.9.1軟件進行網絡的拓撲分析，篩選出核心靶點并繪制蛋白相互作用（PPI）圖；利用David數據庫進行基因本體論（GO）與京都基因和基因組百科全書（KEGG）富集分析，并使用Rstudio軟件對其結果進行可視化；使用AutoDoc 1.5.7軟件對白藜蘆醇與核心靶點進行分子對接；利用UALCAN數據庫驗證核心靶基因在前列腺癌組織中的表達情況。結果 共收集到585個白藜蘆醇作用靶點和5 331個前列腺癌相關靶點，其中交集靶點441個，進一步篩選后得到白藜蘆醇抗前列腺的作用靶點67個，其中核心靶點有腫瘤抑制因子p53（TP53）、蛋白激酶B1（Akt1）、信號轉導和轉錄激活因子3（STAT3）、雌激素受體1（ESR1）、轉錄因子Jun（JUN）、原癌基因酪氨酸蛋白激酶Src（SRC）、連環(huán)蛋白β1（CTNNB1）、絲裂原活化蛋白激酶1（MAPK1）；KEGG富集分析主要得到糖尿病并發(fā)癥中的晚期糖基化終產物及其受體（AGE-RAGE）信號通路、磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信號通路、催乳素信號通路等；分子對接結果顯示，白藜蘆醇和核心靶點之間均具有良好的結合性；核心基因表達量驗證結果表明，TP53和Akt1在前列腺癌組織中表達量較高，STAT3、ESR1、CTNNB1、MAPK1則表達量較低。結論 白藜蘆醇可能通過TP53、Akt1、STAT3、ESR1、JUN等靶點調節(jié)AGE-RAGE、PI3K/Akt等信號通路發(fā)揮抗前列腺癌的作用。

Objective To investigate the potential mechanisms of resveratrol in prostate cancer through the integration of network pharmacology and molecular docking technologies. Methods The target of resveratrol was retrieved and collected from 9 drug target databases including TCMSP, HERB, and Drugbank. The corresponding targets of prostate cancer were obtained by using six disease target databases, such as DisGeNET, GeneCards, and OMIM. The intersection targets of drugs and diseases were obtained using Venny 2.1.0 platform. Then topological analysis was carried out using String database and Centiscape 2.2 plug-in of Cytoscape 3.9.1 software to further screen the anti-prostate action targets of resveratrol. Thirdly, String database and Cytoscape 3.9.1 software were used for topological analysis of the network, core targets were selected, and protein interaction (PPI) diagram was drawn. GO and KEGG enrichment analysis using the David database and visualization of the results using Rstudio software, AutoDoc 1.5.7 software was used for molecular docking of resveratrol with the core target. UALCAN database was used to verify the expression of core target genes in prostate cancer tissues. Results A total of 585 resveratrol action targets and 5 331 prostate cancer-related targets were collected, including 441 overlapping targets. After further screening, 67 resveratrol anti-prostate action targets were obtained. The core targets are TP53, Akt1, STAT3, ESR1, JUN, SRC, CTNNB1, MAPK1. KEGG enrichment analysis mainly obtained the signal pathway of AGE-RAGE, PI3K/Akt, prolactin and so on. The results of molecular docking showed that resveratrol and the core target had good binding property. The results of core gene expression verification showed that TP53 and Akt1 were highly expressed in prostate cancer tissues, while STAT3, ESR1, CTNNB1, and MAPK1 were lower. Conclusion Resveratrol may modulate AGE-RAGE, PI3K/Akt, and other signaling pathways through targets such as TP53, Akt1, STAT3, ESR1, and JUN, thereby exerting anti-prostate cancer effects.

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湖南省自然科學基金資助項目（2024JJ9308）；長沙市科技計劃項目（kq2208112）；湖南省人民醫(yī)院仁術重點項目（RS2022A13）；湖南省衛(wèi)健委科研項目（202204052798）；湖南省衛(wèi)生健康委科研計劃項目（202204053556）；湖南省教育廳科學研究項目（22C0036）；湖南省衛(wèi)生健康高層次人才支持計劃資助項目（湘衛(wèi)函[2023]78號）