基于网络药理学探讨扶正抑瘤方对非小细胞肺癌的作用原理

To Explore the Mechanism of Fuzheng Yiliu Decoction on Non-Small Cell Lung Cancer Based on Network Pharmacology

摘要: 目的：基于网络药理学方法探讨中药复方扶正抑瘤方治疗非小细胞肺癌(NSCLC)的作用原理。方法：用TCMSP数据库收集扶正抑瘤方中各中药里的化学成分，再从TCMSP数据库中检索各化学成分对应的靶标，收集以口服生物利用度(oral bioavailability, OB) ≥ 30%和类药性(Drug-likeness, DL) ≥ 0.18为标准筛选的活性成分及其预测靶标，导入CytoScape Version 3.8.2软件，绘制成分–靶标网络图，得到该方的效应靶标。以“非小细胞肺癌”为关键词，从GeneCards数据库查找疾病靶标，绘制韦恩图。将韦恩图中显示的药物化学成分与疾病的相同基因通过R x64 4.0.5软件转换出其对应的entrezID，进行GO富集分析和KEGG通路分析。再将相同基因导入String数据库进行蛋白–蛋白相互作用分析，获取蛋白相互作用信息后，导入CytoScape Version 3.8.2软件构建蛋白–蛋白相互作用网络。结果：共检索出14个小分子成分，5430个基因靶标，相同靶基因148个，其中度值排名较靠前的蛋白AKT1 (蛋白激酶1)、IL6 (白介素6)、VEGFA (血管内皮生长因子A)、MAPK3 (促分裂原活化蛋白激酶3)、JUN (JUN蛋白)、CASP3 (胱天蛋白酶3)、MYC (癌基因MYC)、EGF (表皮生长因子)、EGFR (表皮生长因子受体)、PTGS2 (人前列腺素内过氧化物合酶)、MAPK1 (丝裂原活化蛋白激酶1)、ESR1 (雌激素受体1)被认为是蛋白相互作用网络中的核心靶点；分析GO生物学过程、分子功能及细胞组分相关条目前20条及KEGG通路前20条，主要涉及癌症通路、MAPK3信号通路及肿瘤坏死因子信号通路、IL-17信号通路等。结论：扶正抑瘤方可能通过多成分、多靶点、多途径参与调控NSCLC细胞增殖与凋亡等多种生理过程，发挥对NSCLC的干预作用。

Abstract: Objective: To explore the mechanism of Fuzheng Yiliu decoction in the treatment of non-small cell lung cancer (NSCLC) based on network pharmacology. Methods: The chemical constituents of fu-zheng antitumor prescription were collected by TCMSP database, and the corresponding targets of chemical constituents were retrieved from TCMSP database. The active ingredients screened based on oral bioavailability (OB) ≥ 30% and drug-like (DL) ≥ 0.18 and their prediction targets are col-lected and imported into CytoScape Version 3.8.2 software. The composition-target network dia-gram is drawn, and the effector target of this square is obtained. Taking “non-small cell lung cancer” as the key word, the disease targets were searched from GeneCards database and a Wayne diagram was drawn. The drug chemical components shown in Wayne diagram and the same gene of the dis-ease were transformed into their corresponding entrezID by R x64 4.0.5 software, and GO enrich-ment analysis and KEGG pathway analysis were performed. Then the same genes were imported into String database for protein-protein interaction analysis. After obtaining the protein interaction information, the same genes were imported into CytoScape Version 3.8.2 software to construct the protein-protein interaction network. Results: A total of 14 small molecular components, 5430 gene targets and 148 identical target genes were retrieved. Among them, AKT1 (protein kinase 1), IL6 (interleukin 6), VEGFA (vascular endothelial growth factor A) and MAPK3 (mitogen-activated pro-tein kinase 3) ranked high in degree value ), JUN (JUN protein), CASP3 (cypsin 3), MYC (oncogene MYC), EGF (epidermal growth factor), EGFR (epidermal growth factor receptor), PTGS2 (human prostaglandin endoperoxide synthase), MAPK1 (mitogen-activated protein kinase 1), ESR1 (estro-gen receptor 1) are considered to be core targets in protein interaction networks; the biological process, molecular function and cell composition of GO were analyzed in 20 related strips and the first 20 KEGG pathways, mainly involving cancer pathway, MAPK3 signaling pathway, tumor necro-sis factor signaling pathway, IL-17 signaling pathway, etc. Conclusion: Fuzheng Yiliu decoction may regulate the proliferation and apoptosis of NSCLC cells through multiple components, multiple tar-gets and multiple pathways, and play an intervention role in NSCLC.