基于网络药理学鉴定人参皂苷Rg3抗卵巢癌的分子靶点研究

Exploring the molecular targets of ginsenoside Rg3 for ovarian cancer treatment based on network pharmacology

目的 通过网络药理学寻找人参皂苷Rg3抑制卵巢癌的可能靶点,探索人参皂苷Rg3抑制卵巢癌的药理机制。方法 利用比较毒理基因组学数据库(CTD)收集人参皂苷Rg3的作用靶点,利用药物靶标数据库(TTD)和基因卡(GeneCards)数据库收集卵巢癌异常表达分子,通过交集分析获得人参皂苷Rg3作用于卵巢癌的可能靶点;对所选靶点进行蛋白质-蛋白质相互作用(PPI)网络构建、基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)信号通路富集分析,选取富集度最高的靶点进行实验,验证人参皂苷Rg3对该靶点表达水平的影响。结果 在CTD数据库中获得人参皂苷Rg3的潜在作用靶点65个,在GeneCards数据库和TTD数据库中搜索到卵巢癌的潜在疾病作用靶点8 412个,共获得4个人参皂苷Rg3与卵巢癌的交集靶点,包括表皮生长因子受体(EGFR)、多聚二磷酸腺苷核糖聚合酶1(PARP1)、含杆状病毒IAP重复序列蛋白5(BIRC5)和凸素1(PROM1)。GO富集分析得到P<0.05的条目共计433个,包括生物过程(BP)条目357个、细胞组成(CC)条目33个、分子功能(MF)条目43个。KEGG信号通路富集分析得到P<0.05的通路共计23条,均与肿瘤发生发展密切相关。蛋白免疫印迹检测结果显示人参皂苷Rg3可显著降低卵巢癌细胞系(3AO、A2780和SKOV3)的EGFR蛋白水平。结论 人参皂苷Rg3可能通过EGFR相关信号通路来抑制卵巢癌的进展。

Objective To explore the potential therapeutic targets and pharmacological mechanisms of ginsenoside Rg3 to inhibit ovarian cancer based on network pharmacology.Methods The targets of ginsenoside Rg3 action were collected using Comparative Toxicogenomics Database(CTD) database, ovarian cancer targets were collected using Therapeutic Target Database(TTD) and Genecards databases, and the possible targets of ginsenoside Rg3 action in ovarian cancer were obtained by intersection analysis using Venn diagram.These targets were subjected to protein-protein interaction(PPI) network construction, gene ontology(GO) enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis to reveal the possible mechanism of action of Rg3 on ovarian cancer.The target gene with the highest enrichment was selected for experimental validation.Results 65 possible targets of ginsenoside Rg3 were obtained from CTD database.8 412 potential ovarian cancer targets were obtained from GeneCards and TTD databases.A total of 4 ginsenoside Rg3 and ovarian cancer intersection targets were obtained, including epidermal growth factor receptor(EGFR),polyadenosine diphosphate ribose polymerase 1(PARP1),baculovirus IAP repeat-containing protein 5(BIRC5) and prominin1(PROM1),GO enrichment analysis showed a total of 433 items with P<0.05,including 357 items for biological process(BP),33 items for cell composition(CC),and 43 items for molecular function(MF).KEEG signaling pathway enrichment analysis showed that there were 23 pathways with P<0.05,all of which were related to the occurrence and development of tumors.Western blotting results showed that Rg3 significantly reduced EGFR protein level of ovarian cancer cell lines(3 AO,A2780 and SKOV3).Conclusion Ginsenoside Rg3 may inhibit the progression of ovarian cancer through EGFR-related signaling pathway.