基于网络药理学与分子对接探讨参芪白石汤治疗胃癌的机制
Exploring the mechanism of Shenqi Baishi Decoction for gastric cancer based on network pharmacology and molecular docking
杨从影 1唐莉华 1孙龙华 2罗江 1黄学娣1
作者信息
- 1. 江西省中西医结合医院 药物临床试验机构办公室,江西 南昌 330002
- 2. 南昌大学第一附属医院 呼吸内科,江西 南昌 330006
- 折叠
摘要
目的 运用网络药理学方法、GEO数据库与分子对接,探讨参芪白石汤(SBD)治疗胃癌(gastric cancer,GC)的作用机制.方法 SBD有效成分及相应靶点通过TCMSP数据库、Pubchem获取,根据《中药大辞典》补充成分,GC差异表达基因从GEO数据库搜索,筛选出 GSE118916 探针芯片数据集,采用STRING数据库构建PPI蛋白-蛋白互作网络,借助Metascape数据库对核心靶点进行GO和KEGG通路富集分析,利用THPA数据库获得核心基因的免疫组化结果及基因蛋白表达,再运用AutoDock分子对接软件对主要活性成分与核心靶点间的相互作用进行验证.结果 获得参芪白石汤 9 味中药,经 OB、DL 初步筛选得到 63 种活性成分,对应 930 个潜在靶点.GO 和KEGG功能富集分析显示,SBD通过平滑肌细胞增殖的调节、对肽的反应、凋亡过程的正向调节、血管相关平滑肌细胞增殖的调节等 14 个生物过程发挥作用,涉及癌症通路、肿瘤坏死因子信号通路、脂质和动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路等.核心基因蛋白的免疫组化显示ICAM1、PTGS2、PPARG在GC组织中呈强阳性表达,分子对接验证发现 3-表齐墩果酸和槲皮素与核心靶点对接良好.结论 多靶点药物SBD可能是一种很有前景的GC治疗候选药物,但还需要进一步的体内体外实验.
Abstract
Objective To investigate the mechanism of action of Shenqi Baishi Decoction(SBD)in the treatment of gastric cancer(GC)using network pharmacology methods,GEO database and molecular docking.Methods The active ingredients and their corresponding targets for SBD were obtained from the TCMSP database and Pubchem.Additional ingredients were included based on the Dictionary of Traditional Chinese Medicines.Differentially expressed genes for GC were identified from the GEO database using the GSE118916 probe microarray dataset.The PPI protein-protein interactions network was constructed using the STRING database.Finally,core targets were analyzed with the assistance of the Metascape database.Pathway enrichment analysis was conducted using GO and KEGG.Immunohistochemistry results for core genes and gene-protein expression were obtained from the THPA database.AutoDock molecular docking software was used to analyze the interactions between the main active ingredients and core targets.Results After screening for OB and DL,63 active ingredients were extracted from 9 herbs of SBD,corresponding to 930 potential targets.The GO and KEGG functional enrichment analyses revealed that SBD acted through 14 biological processes,including the regulation of smooth muscle cell proliferation,response to peptides,positive regulation of apoptotic processes,and regulation of vascular-associated smooth muscle cell proliferation.These processes involved the cancer pathway,tumor necrosis factor signaling pathway,lipids and atherosclerosis,and AGE-RAGE signaling pathway in the complication of diabetes.The immunohistochemistry of the core gene proteins revealed strong positive expression of ICAM1,PTGS2,and PPARG in GC tissues.Molecular docking validation demonstrated that 3-epi-oleanolic acid and quercetin docked well with the core targets.Conclusions Further in vivo and in vitro experiments are needed to determine if the multi-target drug SBD is a promising candidate for GC therapy.
关键词
参芪白石汤/胃癌/GO富集分析/KEGG富集分析/网络药理学Key words
Shenqi Baishi Decoction/gastric cancer/GO enrichment analysis/KEGG enrichment analysis/network phar-macology引用本文复制引用
基金项目
江西省卫生健康委科技计划(202211480)
国家自然科学基金项目(81960523)
出版年
2024
国家科技期刊平台
NSTL
万方数据