基于GEO 数据库差异基因贞芪扶正颗粒治疗肝癌机制研究
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Study on the Mechanism of Zhenqi Fuzheng Granules in the Treatment of Liver Cancer Based on GEO Database
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    摘要:

    目的:基于GEO 数据库和网络药理学探索贞芪扶正颗粒治疗肝癌的作用机制。方法:从GEO 数据库中获取肝癌组织及癌旁正常组织差异基因,从中药系统药理学分析平台(TCMSP) 中获取贞芪扶正颗粒的有效化合物及其作用靶点。构建有效化合物-靶点网络,利用STRING 数据库构建蛋白互作(PPI) 网络,使用R 软件进行GO 富集和KEGG 通路富集分析,并使用Cytoscape 3.8.0 软件构建靶点-信号通路网络图。结果:与癌旁正常组织比较,肝癌组织中高表达的前3 位基因分别是GPC3、SPINK1 和AKR1B10。从TCMSP 数据库中收录黄芪有效成分87 个,女贞子有效成分119 个。网络拓扑学分析发现中心值和度值排名前3 位化合物分别是槲皮素、山柰酚和木犀草素。度值排名前3 位潜在靶点基因分别是CYP1A1、CYP3A4 和CYP1A2。GO富集共获得生物学过程条目273 个,生物学过程主要富集于生物对外来刺激的反应,对金属离子的反应和细胞激素代谢过程。KEGG 通路主要富集于细胞色素P450 的异生素代谢,化学致癌作用和药物代谢-细胞色素。结论:贞芪扶正颗粒可通过多分子、多靶点、多通路影响化疗药物的生物转化、代谢清除和提高对纳米治疗的敏感度,达到辅助治疗肝癌的目的。

    Abstract:

    Abstract:Objective:To explore the mechanism of Zhenqi Fuzheng granules in the treatment of liver cancer based on GEO database and network pharmacology. Methods: The differential genes of liver cancer tissues and adjacent normal tissues were obtained from GEO database,and the effective compounds and action targets of Zhenqi Fuzheng granules were obtained from Systematic Pharmacological Analysis Platform for Traditional Chinese Medicine(TCMSP). Effective compound target network was constructed, protein- protein interaction (PPI) network was constructed by STRING database, GO enrichment and KEGG pathway enrichment were analyzed by R software,and target signal pathway network diagram was constructed by Cytoscape 3.8.0 software. Results: Compared with adjacent normal tissues, the top three genes highly expressed in liver cancer tissue were GPC3, SPINK1 and AKR1B10, respectively. 87 active components of Astragalus membranaceus and 119 active components of Ligustrum lucidum were collected from TCMSP database. Network topology analysis showed that quercetin, kaempferol and luteolin were the top three compounds in center value and degree value, respectively. The top three potential target genes were CYP1A1,CYP3A4 and CYP1A2. A total of 273 biological process items were obtained by go enrichment. The biological process is mainly concentrated in the biological response to external stimuli, metal ions and cytokine metabolism. KEGG pathway is mainly enriched in xenobiotic metabolism of cytochrome P450, chemical carcinogenesis and drug metabolism-cytochrome P450. Conclusion : Zhenqi Fuzheng granules can affect the biotransformation, metabolic clearance of chemotherapeutic drugs and improve the sensitivity to nanotherapy through multiple molecules, multiple targets and multiple pathways, so as to achieve the purpose of adjuvant treatment of liver cancer.

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张金发,杭小凤,李方正,刘伟强.基于GEO 数据库差异基因贞芪扶正颗粒治疗肝癌机制研究[J].新中医,2021,53(21):155-162

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  • 在线发布日期: 2021-11-12
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