“黄芪-半夏”药对治疗非小细胞肺癌作用机制研究

Exploration of Action Mechanism of“Huangqi-Banxia”Drug Pair in Treatment of Non-small Cell Lung Cancer

目的运用网络药理学方法及分子对接技术探讨黄芪-半夏”药对治疗非小细胞肺癌(NSCLC)的作用机制。方法通过文献查找及TCMSP数据库筛选“黄芪-半夏”药对主要成分及作用靶点,在GeneCards、PharmGKB、DrugBank、OMIM数据库获取NSCLC相关靶点,利用Cytoscape软件分别构建“中药-成分-靶点”“中药-成分-靶点-疾病”相互作用网络;运用STRING数据库构建蛋白互作网络,并根据拓扑学参数筛选“黄芪-半夏”药对治疗NSCLC的关键靶点;对关键靶点进行GO功能富集和KEGG通路分析,并构建“成分-靶点-通路”网络图,运用Auto Dock Vina 1.1.2将得到的主要活性成分与关键靶点进行分子对接,运用PyMOL软件进行结果可视化。结果共获得“黄芪-半夏”药对有效成分33个,作用于227个潜在靶点,NSCLC靶点1253个,拓扑分析得到关键靶点97个,其中度值≥中位数的靶点有48个,包括TP53、AKT1、CASP3、JUN等。GO功能富集分析得到生物过程主要涉及细胞因子介导的信号通路,基因表达的正向调控,RNA聚合酶II启动子转录的正调控;KEGG通路富集分析主要包括Pathways in cancer通路、肿瘤坏死因子信号通路、PI3K-Akt通路等,分子对接结果显示,“黄芪-半夏”药对主要活性化合物与5个核心靶点的结合能力皆良好。结论“黄芪-半夏”药对可能通过槲皮素、山奈酚、黄芩素等主要活性成分,作用于TP53、AKT1、CASP3、JUN、VEGFA等相关靶点,干预Pathways in cancer、肿瘤坏死因子、PI3K-Akt等信号通路,协同产生调控肿瘤细胞周期、介导肿瘤细胞凋亡、抑制其增殖分化及转移等来防治NSCLC。

Objective To explore the mechanism of action of Huangqi-Banxia in the treatment of non-small cell lung cancer(NSCLC)using network pharmacology methods and molecular docking technology.Methods Through literature search and TCMSP database screening,the main components and targets of the“Huangqi-Banxia”drug pair were identified.NSCLC related targets were obtained from GeneCards,PharmaGKB,DrugBank,and OMIM databases.The“Traditional Chinese Medicine-Component-Target”and“Traditional Chinese Medicine-Component-Target-Disease”interaction networks were constructed using Cytoscape software;The STRING database was used to construct a protein interaction network,and the key targets of“Huangqi-Banxia”drugs for NSCLC were screened according to topology parameters;Conduct GO functional enrichment and KEGG pathway analysis on key targets,and construct a“component target pathway”network diagram.Use Auto Dock Vina 1.1.2 to connect the main active ingredients obtained with key targets,and use PyMOL software to visualize the results.Results A total of 33 active ingredients were obtained from the“Huangqi-Banxia”drug pair,which acted on 227 potential targets,1253 NSCLC targets,and 97 key targets were identified through topological analysis.Among them,48 targets with degree values≥the median,including TP53,AKT1,CASP3,JUN,etc.GO function enrichment analysis shows that biological processes mainly involve cytokine mediated signal pathways,positive regulation of gene expression,and positive regulation of RNA polymerase II promoter transcription;The enrichment analysis of KEGG pathway mainly includes pathways in cancer pathway,tumor necrosis factor signaling pathway,PI3K Akt pathway,etc.The molecular docking results show that the drug“Huangqi-Banxia”has good binding ability to the main active compounds and five core targets.Conclusion The“Huangqi-Banxia”drug pair may act on TP53,AKT1,CASP3,JUN,VEGFA and other related targets through the main active ingredients such as quercetin,kaempferol,and baicalin,interfering with signaling pathways such as Pathways in cancer,tumor necrosis factor,and PI3K-Akt,synergistically producing and regulating tumor cell cycle,mediating tumor cell apoptosis,inhibiting its proliferation,differentiation,and metastasis to prevent and treat NSCLC.