基于网络药理学可视化及实验验证益肾补血中药治疗前列腺癌的作用机制研究  

Study on The Mechanism of Invigorating Kidney and Blood Chinese Medicine in The Treatment of Prostate Cancer Based on Network Pharmacology Visualization and Experimental Verification

作　　者：刘伟[1] 刘平安 杨磊[2] 郭璇[1] 李媛 唐旖雯 刘德果 LIU Wei;LIU Ping-an;YANG Lei;GUO Xuan;LI Yuan;TANG Yi-wen;LIU De-guo(Hunan University of Traditional Chinese Medicine,Changsha 410208,China;The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine,Changsha 410000,China)

机构地区：[1]湖南中医药大学,长沙410208 [2]湖南中医药大学第一附属医院,长沙410000

出　　处：《中国中医基础医学杂志》2021年第9期1467-1474,共8页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金资助项目(81804075)-基于谱效(毒)相关和PI3K/Akt/mTOR信号通路介导的中药肝毒性物质基础及作用机制研究;湖南省自然科学基金资助项目(2019JJ50436)-中国道地药材信息地图研究;湖南省科技厅科学技术项目(20190733)-基于PI3K/Akt/mTOR信号通路的益肾补血中药治疗前列腺癌作用机制研究;湖南省哲学社会科学基金年度项目(17YBA322)-中国古代针灸信息图表的视觉文化研究。

摘　　要：目的:采用网络药理学研究益肾补血中药治疗前列腺癌的生物学物质基础与药效机制。方法:借助TCMSP、GeneCards等数据库及相关文献构建3味经典益肾补血中药(淫羊藿、三七、当归)治疗前列腺癌的“药物-疾病-靶点”网络,利用STRING及CentiScape插件构建上述药物治疗前列腺癌的蛋白-蛋白相互作用(PPI)网络,同时对关键靶点进行GO功能富集分析以及KEGG信号通路富集分析,并以细胞实验进一步验证网络药理学所得结论。结果:益肾补血中药治疗前列腺癌的“药物-疾病-靶点”网络共涉及148个共同靶点,GO功能富集提示益肾补血中药治疗前列腺癌的生物学过程及功能集中在泛素化、核受体功能、转录相关功能、激素受体功能、细胞凋亡、细胞周期等;KEGG通路富集分析提示益肾补血中药治疗前列腺癌主要涉及细胞凋亡、细胞周期、肿瘤抑制信号通路(p53)、内分泌抵抗、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)、肿瘤坏死因子(TNF)等信号通路。细胞实验结果显示益肾补血中药可有效抑制前列腺癌LNCaP细胞的增殖并促进其凋亡。Western blotting结果显示,益肾补血中药能够调控前列腺癌LNCaP细胞增殖、凋亡以及细胞周期相关蛋白的表达水平。结论:益肾补血中药治疗前列腺癌的作用靶点和药效机制,可能与其调控细胞增殖、凋亡和细胞周期的生物学过程及信号通路相关。Objective:To study the biological material basis and efficacy mechanism of Yishen Buxue Chinese medicine in the treatment of prostate cancer by using network pharmacology.Methods:TCMSP,GeneCards and other databases and related literatures were used to construct a"drug-disease-target"network of 3 classic Chinese medicines for promoting kidney and blood(Epimedium,Sanqi,Angelica)for prostate cancer,and the above drugs were constructed using STRING and CentiScape plugins PPI network for the treatment of prostate cancer,while performing GO function enrichment analysis and KEGG signal pathway enrichment analysis on key targets,and further validating the conclusions obtained by network pharmacology through cell experiments.Results:The"drug-disease-target"network of Yishen Buxue Chinese medicine for prostate cancer involved a total of 148 common targets.The enrichment of GO functions suggests that the biological processes and functions of Yishen Buxue Chinese medicine for prostate cancer are concentrated in ubiquitination,Nuclear receptor function,transcription-related function,hormone receptor function,apoptosis,cell cycle,etc;KEGG pathway enrichment analysis suggests that Yishen Buxue Chinese medicine treatment of prostate cancer mainly involves apoptosis,cell cycle,tumor suppressor signaling pathway(p53),Endocrine resistance,phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT),tumor necrosis factor(TNF)and other signaling pathways.Cell experiment results show that Yishen Buxue Chinese medicine can effectively inhibit the proliferation of prostate cancer LNCaP cells and promote their apoptosis.Western blotting results showed that Yishen Buxue Chinese medicine can regulate the proliferation,apoptosis and cell cycle-related protein expression of prostate cancer LNCaP cells.Conclusion:The target and efficacy mechanism of Yishen Buxue Chinese medicine in the treatment of prostate cancer may be related to its biological processes and signaling pathways that regulate cell proliferation,apoptosis and cell cycle.

关 键 词：网络药理学 益肾补血中药 前列腺癌 药效机制 中医药研究 

分 类 号：R737.25[医药卫生—肿瘤]