结合网络药理学和分子对接技术探讨党参-多序岩黄芪-白术治疗肺癌的药理机制。
Combining network pharmacology and molecular docking to explore the pharmacological mechanism of Codonopsis Radix.-Hedysarum Multijugum Maxim.-Atractylodes Macrocephala Koidz. in treating lung cancer.
作者信息
He Bin, Cui Jun, Zhang Zengwang, Zhang Yongjun
机构信息
Department of Cardiothoracic Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, No.136, Jingzhou Street, Xiangyang, Hubei, 441021, People's Republic of China.
出版信息
BMC Complement Med Ther. 2025 Feb 21;25(1):66. doi: 10.1186/s12906-025-04823-z.
AIM
To explore the potential mechanism of the treatment of lung cancer (LC) with Codonopsis Radix.-Hedysarum Multijugum Maxim.-Atractylodes Macrocephala Koidz. (CHA).
METHODS
The active ingredients and targets of CHA were obtained from TCMSP and SwissTargetPrediction databases. LC-related genes were obtained from MalaCards, GeneCards and DisGenNET databases. A protein-protein interaction network was constructed using STRING database, and analyzed with Cystoscape software. The core targets of CHA in LC treatment were determined by topological analysis, and functional annotation of these targets was performed via Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The binding ability of the target to the active ingredient was evaluated by molecular docking. CCK-8 assay, Transwell assay, qRT-PCR, Western blot and lung metastasis model in nude mice were used to evaluate the effects of CHA on the viability, migration and invasion of LC cells.
RESULTS
27 active components and 411 common targets of CHA in lung cancer treatment were obtained. The common targets were associated multiple biological processes and pathways including PI3K-AKT pathway. 12-senecioyl-2E,8E,10E-atractylentriol, 14-acetyl-12-senecioyl-2E,8Z,10E-atractylentriol, astrapterocarpan, isoflavanone, (R)-Isomucronulatol were identified as the main bioactive components of CHA, and SRC, HSP90AA1, AKT1, EGFR, ESR1 were identified as core targets of CHA in LC treatment. The bioactive ingredients had good binding ability with the core targets. CHA significantly inhibited the viability, migration and invasion of LC cells, and also suppressed the transcription of core genes, and repressed the activation of PI3K/AKT pathway.
CONCLUSION
For LC, CHA exerts tumor-suppressive effects through various bioactive components, acting on multiple targets and signaling pathways.
目的
探讨党参-多序岩黄芪-白术（CHA）治疗肺癌（LC）的潜在机制。
方法
从中药系统药理学数据库与分析平台（TCMSP）和瑞士药物靶点预测数据库获取CHA的活性成分和靶点。从MalaCards、基因卡片（GeneCards）和疾病基因网络（DisGenNET）数据库获取LC相关基因。使用STRING数据库构建蛋白质-蛋白质相互作用网络，并用Cytoscape软件进行分析。通过拓扑分析确定CHA在LC治疗中的核心靶点，并通过基因本体（GO）分析和京都基因与基因组百科全书（KEGG）分析对这些靶点进行功能注释。通过分子对接评估靶点与活性成分的结合能力。采用CCK-8法、Transwell法、qRT-PCR、蛋白质免疫印迹法以及裸鼠肺转移模型评估CHA对LC细胞活力、迁移和侵袭的影响。
结果
获得了CHA在肺癌治疗中的27种活性成分和411个共同靶点。这些共同靶点与包括PI3K-AKT通路在内的多个生物学过程和途径相关。12-千里光酰基-2E,8E,10E-白术内酯三醇、14-乙酰基-12-千里光酰基-2E,8Z,10E-白术内酯三醇、紫穗槐二氢黄酮、异黄酮、（R）-异鼠李素被确定为CHA的主要生物活性成分，而原癌基因酪氨酸蛋白激酶（SRC）、热休克蛋白90α家族成员1（HSP90AA1）、蛋白激酶B1（AKT1）、表皮生长因子受体（EGFR）、雌激素受体1（ESR1）被确定为CHA在LC治疗中的核心靶点。生物活性成分与核心靶点具有良好的结合能力。CHA显著抑制LC细胞的活力、迁移和侵袭，还抑制核心基因的转录，并抑制PI3K/AKT通路的激活。
结论
对于LC，CHA通过多种生物活性成分发挥肿瘤抑制作用，作用于多个靶点和信号通路。
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