基于网络药理学与分子对接技术探讨石上柏在治疗癌症中的作用机制  

Study on the Mechanism of Selaginella Doederleinii Hieron in Treating Cancer Based on Network Pharmacology and Molecular Docking Technology

作　　者：武乐[1] 黄淑娟[1] 余腾骅 邱宇安[1] 方义文 梁群 何芳 刘利艳[1] WU Le;HUANG Shujuan;YU Tenghua(Jiangxi Cancer Hospital,Nanchang,330029)

机构地区：[1]江西省肿瘤医院,330029

出　　处：《实用癌症杂志》2022年第12期1961-1966,共6页The Practical Journal of Cancer

基　　金：江西省卫生健康委员会科技计划项目(编号:202130722,202211027);江西省中医药管理局科技计划项目(编号:2021A341)。

摘　　要：目的采用网络药理学和分子对接技术分析方法,建立石上柏治疗癌症的“化合物-靶标-疾病-通路”作用网络,探索石上柏抗肿瘤作用机制。方法通过中药系统药理学分析平台TCMSP数据库收集石上柏的所有活性成分;根据类药性(DL)及口服生物利用度(OB)相关条件筛选,获得活性成分;通过PubChem和swisstarget数据库寻找经筛选后活性成分的预测靶点,在疾病靶点数据库DisGeNET和Genecards、数据交集数据库Draw Venn Diagram搜索共同靶基因;通过String网络平台与Cytoscape软件结合,绘制蛋白相互作用网络,归纳总结石上柏的主要潜在靶点;通过KEGG通路进行富集和生物学分析、采用分子对接软件DISCOVERY STUDIO对潜在的作用靶点(靶点数目最多的活性成分和蛋白相互作用中自由度最大的蛋白质)进行验证。结果石上柏预测靶点与癌症靶点的交叉靶点共有78个,主要活性成分可能为芹菜素、(6-[5-(5,7-二羟基-4-酮-色烯-2-基)-2-甲氧基-苯基]-5,7-二羟基-2-(4-羟基苯基)色酮)和谷甾醇,核心靶点为血管内皮生长因子A(VEGFA)、蛋白激酶1(AKT1)、表皮生长因子受体(EGFR)、雌激素受体1(ESR1)、Src蛋白(SRC)、前列腺素内过氧化物合酶2(PTGS2)等;经通路分析发现共涉及通路42条,其中19条通路与癌症相关;分子对接显示石上柏中(6-[5-(5,7-二羟基-4-酮-色烯-2-基)-2-甲氧基-苯基]-5,7-二羟基-2-(4-羟基苯基)色酮)、芹菜素能与AKT1、VEFGA稳定结合,并分别通过HIS A56、GLY A24、LYS A41,GLN E112、GLN E39、GLN F39;LYS B43、GLN A39、GLU B166,GLU A60、LYS A41和PHE A23等氨基酸残基进行相互作用。结论该研究揭示了石上柏治疗癌症是基于潜在的多成分、多靶点、多通路的相互协作作用机制。Objective To establish a network of“compound-target-disease-pathway”for the treatment of cancer based on network pharmacology and molecular docking techniques to explore the mechanism of anti-tumor effect of Selaginella Doederleinii Hieron.Methods All ingredients of Selaginella Doederleinii Hieron were collected from TCMSP database of Chinese medicine system pharmacology analysis platform.The active ingredients were screened according to drug-like(DL)and oral bioavailability(OB)conditions.The predicted targets of active components were searched by PubChem and swisstarget database.The disease targets were collected in disease target data DisGeNET and Genecards,the common targets were acquired in Draw Venn Diagram database,Combined the String network platform with Cytoscape software to summarize the main potential targets of Selaginella Doederleinii Hieron..Enrichment and biological analysis were performed by the KEGG pathway,and the molecular docking software DISCOVERY STUDIO was used to validate the potential target(the active component with the highest number of targets and the most frequency in protein interaction).Results There were 78 common targets for the predicted target and cancer crossover,and the main active ingredient might be apigenin,(6-[5-(5,7-dihydroxy-4-keto-chromen-2-yl)]-2-methoxy-phenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)chromone)and sitosterol,the core target is vascular endothelial growth factor A(VEGFA),protein kinase B(AKT1),epidermal growth factor receptor(EGFR),estrogen receptor 1(ESR1),Src protein(SRC),prostaglandin endoperoxide synthase 2(PTGS2),etc.A total of 42 pathways were involved and 19 pathways of that were related to cancer.Molecu-lar docking revealed that(6-[5-(5,7-dihydroxy-4-keto-chromen-2-yl)-2-methoxy-phenyl]-5,7-dihydroxy-2-(4-Hydroxyphenyl)chromone),apigenin can stably bind to AKT1,VEFGA,and interact with each other through amino acid residues HIS A56,GLY A24,LYS A41,GLN E112,GLN E39,GLN F39;LYS B43,GLN A39,GLU B166,GLU A60,LYS A41,and PHE A23.Conclusions This study re

关 键 词：网络药理学 分子对接 石上柏 癌症 

分 类 号：R730.52[医药卫生—肿瘤]