基于网络药理学及体外实验探讨人参-甘草对非小细胞肺癌的作用机制

周文月; 文艺儒; 周森林; 王梦琪; 童宇; 许光亚; 时政

doi:10.13386/j.issn1002-0306.2022100268

基于网络药理学及体外实验探讨人参-甘草对非小细胞肺癌的作用机制

Study on the Mechanism of Ginseng and Liquorice on Non-small Cell Lung Cancer Based on Network Pharmacology and in Vitro Experiments

摘要

摘要: 目的：本文旨在通过网络药理学及体外实验验证，探讨人参-甘草治疗非小细胞肺癌（NSCLC）的潜在机制及初步药效作用。方法：首先利用中药系统药理学数据库与分析平台（TCMSP）筛选出人参-甘草的活性成分和潜在靶点。通过数据库TTD（Therapeutic Target Database）、CTD（Comparative Toxicogenomics Database）和Gene Cards（The Human Gene Database）获得NSCLC的靶点，进而获取疾病-药物的交集靶点。利用数据库STRING和Cytoscape 3.7.1软件建立蛋白相互作用网络（PPI）。通过基因本体（GO）分析和京都基因与基因组百科全书（KEGG）富集分析确定人参-甘草治疗NSCLC的主要通路与关键靶点。最后利用MTT比色法及流式细胞术验证人参-甘草抗肿瘤作用。结果：通过TTD、CTD和Gene Cards筛选，得到人参-甘草作用于NSCLC的交集靶点122个。从STRING数据库构建的PPI网络中可以得出，其中的苏氨酸蛋白激酶（AKT1）、细胞性肿瘤抗体P53（TP53）、半胱天冬酶3（CASP3）、血管内皮生长因子A（VEGFA）可能成为治疗NSCLC的关键靶点。通过PPI、GO和KEGG综合分析，确定人参-甘草作用NSCLC的关键靶点为AKT1、TP53、IL、AMPK、TNF。体外实验结果显示人参-甘草能显著抑制人非小细胞肺癌细胞增殖，并能诱导肿瘤细胞凋亡，从而发挥抗肿瘤作用。结论：本研究初步探讨了人参-甘草活性成分对NSCLC的潜在机制及初步药效作用，为临床上应用人参-甘草治疗非小细胞肺癌提供新的理论依据。

Abstract: Objective: The study was to investigate the potential mechanisms and preliminarily pharmacological effects of ginseng-licorice in the treatment of non-small cell lung cancer (NSCLC) by network pharmacology and in vitro experiments. Methods: Firstly, the active components and potential targets of ginseng-licorice were screened by using the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP), and the drug-components-target map was constructed using Cytoscape 3.7.1 software. TDD (Therapeutic Target Database), CTD (Comparative Toxicogenomics Database) and Gene Cards (The Human Gene Database) were used to obtain targets for NSCLC, and disease-drug intersection targets were obtained. Protein Interaction Network (PPI) was established by database STRING and Cytoscape software. Combined with PPI, GO and KEGG, the overall analysis was conducted to determine the main pathway and key targets of ginseng-licorice in the treatment of NSCLC. Finally, the anti-tumor effect of ginseng-licorice on NSCLC was verified by MTT colorimetric assay and flow cytometry. Results: The AKT1, TP53, CASP3 and VEGFA should be the potential targets for the treatment of NSCLC 122 targets of "ginseng-licorice" -NSCLC intersection was obtained from the screening of TTD, CTD and gene cards databases. Combined with the comprehensive analysis of PPI, GO and KEGG, the key targets of ginseng and licorice on NSCLC were identified as AKT1, TP53, IL, AMPK and TNF. The results of in vitro experiments showed that the drug to ginseng-licorice could significantly inhibit the proliferation of human non-small cell lung cancer cells, and could induce tumor cell apoptosis, thereby exerting an anti-tumor effect. Conclusion: This study initially explored the potential mechanisms and preliminarily pharmacological effects of the active ingredients of ginseng-licorice on NSCLC, providing a new theoretical basis for the clinical application of drug for the treatment of ginseng-licorice in the treatment of non-small cell lung cancer.