首页|基于网络药理学探讨西黄丸通过EGFR/AKT/P65信号通路抑制肺癌A549细胞侵袭转移的作用

基于网络药理学探讨西黄丸通过EGFR/AKT/P65信号通路抑制肺癌A549细胞侵袭转移的作用

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目的:通过网络药理学和体外实验探讨西黄丸抑制肺癌A549细胞侵袭转移的药效学作用及机制。方法:通过检索TCMSP、TCMID、PubChem数据库筛选西黄丸有效成分及其靶点;搜索GeneCard数据库、OMIM数据库和DrugBank数据库获取肺癌转移的靶点;将药物成分对应靶点与肺癌转移相关的全部靶点取交集,导入Cytoscape 3。8。0软件构建化合物-靶点网络,筛选出西黄丸抗肺癌转移的核心靶点,构建PPI网络;利用R Project软件及Bioconductor数据库、ClusterProfiler程序对共有靶点进行GO和KEGG富集分析;通过划痕愈合实验和Tran-swell 侵袭实验,评价西黄丸含药 血清抑制肺癌 A549细胞侵袭迁移 的作用;利用Western blotting法检测西黄丸含药血清对肺癌A549细胞EGFR、AKT、P65蛋白表达的影响。结果:网络药理学研究获得西黄丸中66个主要活性成分,药物-疾病共同靶点303个,筛选得到核心基因AKT1、JUN、TP53、EGFR、RELA、PIK3CA等;GO和KEGG通路富集分析显示主要信号通路有PI3K/Akt信号通路、TNF信号通路、EGFR信号通路等。体外细胞实验结果显示西黄丸含药血清能降低肺癌A549细胞的划痕愈合率(P<0。05),减少肺癌A549细胞侵袭人工基底膜(P<0。01),并能够抑制EGFR、Akt、P65蛋白的表达(P<0。01或P<0。05)。结论:西黄丸可能通过抑制EGFR/AKT/P65信号通路起到抑制肺癌侵袭转移的生物学效应。
The Inhibitory Effect of Xihuang Pill(西黄丸)on the Metastasis of A549 Cell Via the EGFR/AKT/p65 Pathway Based on Network Pharmacology
Objective:To explore the pharmacodynamic effect and mechanism of Xihuang pill on inhibiting invasion and migration of lung cancer A549 cells by using network pharmacology and in vitro experiments.Methods:The active ingredients of Xihuang pill and their related targets were screened by searching TCMSP,TCMID and PubChem databases.The targets of lung cancer metastasis were obtained by searching the GeneCard database,OMIM database and DrugBank database.The intersection method was used to the related targets of Xihuang pill and the targets of lung cancer metastasis.Cytoscape3.8 software was used to construct the compound-target network and build a PPI network.GO and KEGG enrichment analysis was performed on the intersection targets using the R Project software,Bioconductor database and ClusterProfiler.The methods of cell scratch test and Transwell chamber test were used to evaluate the inhibitory effect of Xihuang pill on the invasion and migration of A549 cells.The method of Western blotting was used to detect the expression of EGFR,AKT and P65 proteins in lung cancer A549 cells.Results:Totally 66 main active ingredients were obtained from Xihuang pill through network pharmacology study.There were 303 common targets of drug-disease screened in Xihuang pill and the key targets involved AKT1,JUN,TP53,EGFR,RELA,PIK3CA and so on.GO and KEGG pathway enrichment analysis showed that the main signaling pathways were PI3K/Akt signaling pathway,TNF signaling pathway,EGFR signaling pathway and so on.In vitro study showed that the Xihuang pill containing serum significantly inhibited the scratch healing rate of A549 cells(P<0.05),reduced the invasion of A549 cells(P<0.01),and inhibited the expression of EGFR,Akt and P 65 proteins(P<0.0l or P<0.05).Conclusion:Xihuang pill may exert biological effects on inhibiting the invasion and metastasis of lung cancer by inhibiting the EGFR/AKT/P65 signaling pathway.

lung cancerXihuang pillmetwork pharmacologyinvasion and migrationA549 cellEGFR

黄倩、张瀚涛、张晓笛、李晋生、徐意

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北京同仁堂科技发展股份有限公司制药厂,北京 100079

北京中研同仁堂医药研发有限公司/中药复方新药开发国家工程研究中心,北京 100079

肺癌 西黄丸 网络药理学 侵袭迁移 A549细胞 EGFR

2024

中医药导报
湖南省中医药学会 湖南省中医管理局

中医药导报

CSTPCD
影响因子:0.952
ISSN:1672-951X
年,卷(期):2024.30(6)
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