红豆杉（TC）在缓解非小细胞肺癌（NSCLC）方面具有巨大的治疗潜力，但TC的作用机制仍不清楚。本研究采用综合生物信息学和网络药理学来探索TC抗NSCLC的潜在靶点和分子机制。从公共数据库获得的数据与适当的生物信息学工具相结合，以确定 TC 和 NSCLC 的共同靶点。共同目标被上传到 Metascape 数据库，用于基因本体术语和京都基因和基因组百科全书途径分析。建立蛋白质-蛋白质相互作用网络，并进行拓扑分析以获得枢纽基因。使用人类蛋白质图谱数据库和适当的生物信息学工具证实了 NSCLC 组织中 hub 基因的表达及其对 NSCLC 患者预后的影响。使用分子对接来验证活性成分和中心靶标之间的结合亲和力。我们发现了 401 个常见靶标，这些靶标在癌症、MAPK 信号传导和 PI3K/Akt 信号传导通路中显着富集。原癌基因酪氨酸蛋白激酶 Src (SRC)、丝裂原激活蛋白激酶 1、磷酸肌醇 3-激酶、调节亚基 1 (PIK3R1)、AKT 丝氨酸/苏氨酸激酶 1 (AKT1)、磷脂酰肌醇 4,5-二磷酸 3 -激酶催化亚基α（PIK3CA）和淋巴细胞特异性蛋白酪氨酸激酶被确定为枢纽基因。免疫组织化学结果证实，NSCLC组织中SRC、丝裂原激活蛋白激酶1、PIK3R1、AKT1和磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α的表达上调，而生存分析显示SRC、 AKT1、PIK3R1和淋巴细胞特异性蛋白酪氨酸激酶与NSCLC患者的预后密切相关。分子对接结果证实 TC 中存在的所有生物活性成分均与枢纽靶点紧密结合。我们的结论是，TC 通过多靶点组合和多途径协同发挥抗 NSCLC 作用。版权所有 © 2023 作者。由 Wolters Kluwer Health, Inc. 出版

Taxus chinensis (TC) has tremendous therapeutic potential in alleviating non-small cell lung cancer (NSCLC), but the mechanism of action of TC remains unclear. Integrated bioinformatics and network pharmacology were employed in this study to explore the potential targets and molecular mechanism of TC against NSCLC. Data obtained from public databases were combined with appropriate bioinformatics tools to identify the common targets for TC and NSCLC. Common targets were uploaded to the Metascape database for gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway analyses. A protein-protein interaction network was established, and topological analysis was performed to obtain hub genes. The expression of the hub genes in NSCLC tissues and their consequent effects on the prognosis of patients with NSCLC were confirmed using the Human Protein Atlas database and appropriate bioinformatics tools. Molecular docking was used to verify the binding affinity between the active ingredients and hub targets. We found 401 common targets that were significantly enriched in the cancer, MAPK signaling, and PI3K/Akt signaling pathways. Proto-oncogene tyrosine-protein kinase Src (SRC), mitogen-activated protein kinase 1, phosphoinositide-3-kinase, regulatory subunit 1 (PIK3R1), AKT serine/threonine kinase 1 (AKT1), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and lymphocyte-specific protein tyrosine kinase were identified as the hub genes. Immunohistochemical results confirmed that the expression of SRC, mitogen-activated protein kinase 1, PIK3R1, AKT1, and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha was upregulated in the NSCLC tissues, while survival analysis revealed the expression of SRC, AKT1, PIK3R1, and lymphocyte-specific protein tyrosine kinase was closely related to the prognosis of patients with NSCLC. Molecular docking results confirmed all bioactive ingredients present in TC strongly bound to hub targets. We concluded that TC exhibits an anti-NSCLC role through multi-target combination and multi-pathway cooperation.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.