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一个药物-生物标志物相互作用模型,用于预测黄芩在不良风险急性髓系白血病中的关键靶点。

A drug-biomarker interaction model to predict the key targets of Scutellaria barbata D. Don in adverse-risk acute myeloid leukaemia.

机构信息

Shandong University of Traditional Chinese Medicine, Jinan, 250014, Shandong Province, People's Republic of China.

Central Laboratory of Affiliated Hospital of Shandong, University of Traditional Chinese Medicine, Jinan, 250014, Shandong Province, People's Republic of China.

出版信息

Mol Divers. 2021 Nov;25(4):2351-2365. doi: 10.1007/s11030-020-10124-z. Epub 2020 Jul 16.

Abstract

A poor prognosis, relapse and resistance are burning issues during adverse-risk acute myeloid leukaemia (AML) treatment. As a natural medicine, Scutellaria barbata D. Don (SBD) has shown impressive antitumour activity in various cancers. Thus, SBD may become a potential drug in adverse-risk AML treatment. This study aimed to screen the key targets of SBD in adverse-risk AML using the drug-biomarker interaction model through bioinformatics and network pharmacology methods. First, the adverse-risk AML-related critical biomarkers and targets of SBD active ingredient were obtained from The Cancer Genome Atlas database and several pharmacophore matching databases. Next, the protein-protein interaction network was constructed, and topological analysis and pathway enrichment were used to screen key targets and main pathways of intervention of SBD in adverse-risk AML. Finally, molecular docking was implemented for key target verification. The results suggest that luteolin and quercetin are the main active components of SBD against adverse-risk AML, and affected drug resistance, apoptosis, immune regulation and angiogenesis through the core targets AKT1, MAPK1, IL6, EGFR, SRC, VEGFA and TP53. We hope the proposed drug-biomarker interaction model provides an effective strategy for the research and development of antitumour drugs.

摘要

预后不良、复发和耐药性是治疗高危急性髓系白血病(AML)的棘手问题。作为一种天然药物,半枝莲(Scutellaria barbata D. Don,SBD)在多种癌症中表现出令人印象深刻的抗肿瘤活性。因此,SBD 可能成为治疗高危 AML 的潜在药物。本研究旨在通过生物信息学和网络药理学方法,利用药物-生物标志物相互作用模型筛选 SBD 在高危 AML 中的关键靶点。首先,从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库和几个药效团匹配数据库中获取与 SBD 活性成分相关的高危 AML 关键生物标志物和靶点。然后,构建蛋白质-蛋白质相互作用网络,并进行拓扑分析和通路富集,以筛选 SBD 干预高危 AML 的关键靶点和主要通路。最后,进行分子对接以验证关键靶点。结果表明,木犀草素和槲皮素是 SBD 治疗高危 AML 的主要活性成分,通过核心靶点 AKT1、MAPK1、IL6、EGFR、SRC、VEGFA 和 TP53 影响耐药性、细胞凋亡、免疫调节和血管生成。我们希望所提出的药物-生物标志物相互作用模型为抗肿瘤药物的研发提供有效策略。

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