目的 基于网络药理学和分子对接技术探究白藜芦醇治疗前列腺癌的潜在作用机制。方法 通过TCMSP、HERB、Drugbank等9个药物靶点数据库检索并收集白藜芦醇的作用靶点；利用DisGeNET、GeneCards、OMIM等6个疾病靶点数据库获得前列腺癌的相应靶点；利用Venny 2.1.0平台获得药物和疾病的交集靶点，然后利用String数据库和Cytoscape 3.9.1软件的Centiscape 2.2插件进行拓扑分析，进一步筛选得到白藜芦醇抗前列腺的作用靶点；再次利用String数据库和Cytoscape 3.9.1软件进行网络的拓扑分析，筛选出核心靶点并绘制蛋白相互作用（PPI）图；利用David数据库进行基因本体论（GO）与京都基因和基因组百科全书（KEGG）富集分析，并使用Rstudio软件对其结果进行可视化；使用AutoDoc 1.5.7软件对白藜芦醇与核心靶点进行分子对接；利用UALCAN数据库验证核心靶基因在前列腺癌组织中的表达情况。结果 共收集到585个白藜芦醇作用靶点和5 331个前列腺癌相关靶点，其中交集靶点441个，进一步筛选后得到白藜芦醇抗前列腺的作用靶点67个，其中核心靶点有肿瘤抑制因子p53（TP53）、蛋白激酶B1（Akt1）、信号转导和转录激活因子3（STAT3）、雌激素受体1（ESR1）、转录因子Jun（JUN）、原癌基因酪氨酸蛋白激酶Src（SRC）、连环蛋白β1（CTNNB1）、丝裂原活化蛋白激酶1（MAPK1）；KEGG富集分析主要得到糖尿病并发症中的晚期糖基化终产物及其受体（AGE-RAGE）信号通路、磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号通路、催乳素信号通路等；分子对接结果显示，白藜芦醇和核心靶点之间均具有良好的结合性；核心基因表达量验证结果表明，TP53和Akt1在前列腺癌组织中表达量较高，STAT3、ESR1、CTNNB1、MAPK1则表达量较低。结论 白藜芦醇可能通过TP53、Akt1、STAT3、ESR1、JUN等靶点调节AGE-RAGE、PI3K/Akt等信号通路发挥抗前列腺癌的作用。

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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湖南省自然科学基金资助项目（2024JJ9308）；长沙市科技计划项目（kq2208112）；湖南省人民医院仁术重点项目（RS2022A13）；湖南省卫健委科研项目（202204052798）；湖南省卫生健康委科研计划项目（202204053556）；湖南省教育厅科学研究项目（22C0036）；湖南省卫生健康高层次人才支持计划资助项目（湘卫函[2023]78号）