| 引用本文:苏晓鹏1，2，晏军1，张潞潞3，李玲孺2，党志博1，李玲1，周怡驰1，胡世平4.基于网络药理学探讨黄芪-丹参药对治疗肝癌的作用机制与实验验证[J].世界中医药,2022,(24):. |
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| 基于网络药理学探讨黄芪-丹参药对治疗肝癌的作用机制与实验验证 |
| Mechanism of Huangqi-Dashen in the Treatment of Liver Cancer Based on Network Pharmacology and Experimental Verification |
| 投稿时间：2020-10-29 |
| DOI：10.3969/j.issn.1673-7202.2022.24.004 |
| 中文关键词: 黄芪 丹参 药对 肝癌 网络药理学 作用机制 靶点 PI3K/AKT信号通路 |
| English Keywords:Huangqi Danshen Herbal pair Liver cancer Network pharmacology Mechanism Target PI3K-AKT signaling pathway |
| 基金项目:国家自然科学基金面上项目（81973733）；广东省自然科学基金面上项目（2019A1515011555） |
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| 中文摘要: |
| 目的：基于网络药理学探讨黄芪-丹参药对治疗肝癌的作用机制，并以体外实验对相关通路进行验证。方法：利用中药系统药理学数据库与分析平台（TCMSP）及相关文献搜集黄芪、丹参的有效成分及相关蛋白质靶点名，利用Unitprot数据库对蛋白质靶点进行基因名校正，并通过Cytoscape 3.8.0软件绘制中药-成分-靶点网络图。通过Drugbank数据库、人类孟德尔遗传数据库（OMIM）、治疗靶点数据库（TTD）、GeneCard数据库搜集肝癌的基因靶点，与黄芪-丹参药对基因靶点取交集后得到核心靶点。随后利用String 11.0数据库、Metascape数据库对核心靶点分别进行蛋白质-蛋白质相互作用（PPI）分析和基因本体（GO）富集分析和京都基因和基因组百科全书（KEGG）富集分析。最后通过CCK-8实验及流式凋亡实验检测药物对肝癌细胞的药效及PCR实验检测PI3K、AKT基因表达水平。结果：共筛选出黄芪丹参药对有效成分76个以及118个核心靶点，经过PPI分析，黄芪丹参药对治疗肝癌可能与AKT1、JUN、MAPK1、MAPK8、IL6、MAPK14、FOS、ESR1、EGFR、CCND1等靶点相关。GO及KEGG富集分析发现，黄芪丹参药对主要作用于转录因子，参与细胞凋亡过程，通过癌症相关通路、PI3K/AKT信号通路及TNF信号通路等起效。CCK-8实验、流式凋亡实验以PCR实验表明黄芪丹参药药对对肝癌有效，并且通过P13K/AKT信号通路发挥凋亡作用。结论：黄芪-丹参药对治疗肝癌具有多成分、多靶点、多通路协同作用的特点，而PI3K/AKT信号通路在其中发挥重要作用。 |
| English Summary: |
| To explore the mechanism of Huangqi(Astragali Radix)-Danshen(Salviae Miltiorrhizae Radix et Rhizoma) in the treatment of liver cancer based on network pharmacology and verify the related pathways by in vitro experiments.Methods:The active ingredients of Huangqi and Danshen and related protein target names were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and related literature.Unitprot database was used to correct the gene names of the protein targets，and Cytoscape3.8.0 software was used to plot the drug-component-target network diagram.The gene targets of liver cancer were collected through the Drugbank，Online Mendelian Inheritance in Man(OMIM)，Therapeutic Target Database(TTD)，and GeneCard，and intersected with gene targets of Huangqi-Danshen to obtain the common targets.Core targets were subjected to protein-protein interaction(PPI) analysis，Gene Ontology(GO) enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses using String 11.0 database and Metascape database，respectively.Finally，the efficacy of the drugs on liver cancer cells was detected by CCK-8 assay and flow cytometry assay，and the expression levels of PI3K and AKT genes were detected by PCR assay.Results:Seventy-six active ingredients and 118 core targets of Huangqi and Danshen were screened out.After PPI analysis，Huangqi and Danshen in the treatment of liver cancer might be related to targets，such as AKT1，JUN，MAPK1，MAPK8，IL6，MAPK14，FOS，ESR1，EGFR，and CCND1.GO and KEGG enrichment analyses showed that Huangqi and Danshen mainly acted on transcription factors，participated in the process of apoptosis，and acted through cancer-related pathways，PI3K-AKT pathway，and TNF signaling pathway.CCK-8 assay，flow cytometry assay，and PCR assay showed that Huangqi and Danshen were effective in the treatment of liver cancer and exerted an apoptotic effect through the P13K-AKT signaling pathway.Conclusion:Huangqi-Danshen herbal pair has the characteristics of a multi-component，multi-target，and multi-pathway synergistic effect in the treatment of liver cancer，where the PI3K-AKT signaling pathway plays an important role. |
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