Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China.
The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
Medicine (Baltimore). 2023 Nov 3;102(44):e35826. doi: 10.1097/MD.0000000000035826.
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.
紫杉醇（TC）在缓解非小细胞肺癌（NSCLC）方面具有巨大的治疗潜力，但 TC 的作用机制尚不清楚。本研究采用整合生物信息学和网络药理学方法，探讨 TC 治疗 NSCLC 的潜在靶点和分子机制。从公共数据库中获取数据，并结合适当的生物信息学工具，鉴定 TC 和 NSCLC 的共同靶点。将共同靶点上传至 Metascape 数据库进行基因本体论术语和京都基因与基因组百科全书通路分析。构建蛋白质-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，验证 NSCLC 组织中枢纽基因的表达及其对 NSCLC 患者预后的影响。采用分子对接验证活性成分与枢纽靶点的结合亲和力。我们发现 401 个共同靶点，这些靶点在癌症、MAPK 信号和 PI3K/Akt 信号通路中显著富集。原癌基因酪氨酸蛋白激酶 Src（Src）、丝裂原活化蛋白激酶 1、磷酸肌醇-3-激酶，调节亚基 1（PIK3R1）、蛋白激酶 B1（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鉴定为枢纽基因。免疫组织化学结果证实，Src、丝裂原活化蛋白激酶 1、PIK3R1、AKT1 和磷脂酰肌醇-4,5-二磷酸 3-激酶催化亚基α在 NSCLC 组织中的表达上调，而生存分析表明，Src、AKT1、PIK3R1 和淋巴细胞特异性蛋白酪氨酸激酶的表达与 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强烈结合。综上所述，TC 通过多靶点结合和多途径协同作用发挥抗 NSCLC 作用。
