| 摘要: |
| 目的：基于网络药理学和分子对接技术分析益气续骨合剂治疗乳腺癌骨转移的作用机制。方法：通过中药系统药理学数据库与分析平台（Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP）和中医百科全书（The Encyclopedia of Traditional Chinese Medicine，ETCM）平台获取益气续骨合剂的活性成分及靶点；从癌症基因组图谱（The Cancer Genome Atlas，TCGA）数据库下载乳腺癌骨转移、非骨转移及正常样本转录组数据，筛选差异基因（P<0.01）；取药物靶点与疾病靶点交集，构建药物-成分-靶点网络。对关键靶点进行基因本体（gene ontology，GO）功能注释和京都基因与基因组数据库（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析，蛋白质-蛋白质相互作用（Protein Protein Interaction，PPI）网络筛选hub基因，分子对接验证结合活性。结果：获得药物靶点254个、疾病靶点12 129个，交集靶点181个。富集分析结果显示，靶点涉及氧化应激、炎症反应、磷脂酰肌醇3-激酶-蛋白激酶B信号通路（PI3K-AKT）等。PPI网络确定丝氨酸-苏氨酸蛋白激酶（AKT Serine/Threonine Kinase 1，AKT1）、白蛋白（Albumin，ALB）、原癌蛋白JUN（Jun Proto-Oncogene，JUN）、白细胞介素-6（interleukin 6，IL-6）、β-连环蛋白（Catenin Beta 1，CTNNB1）为hub基因。分子对接证实槲皮素（与AKT1、JUN、IL-6结合）和β-胡萝卜素（与ALB结合）为关键活性成分（结合能<-3.42 kcal/mol）。结论：益气续骨合剂可能通过槲皮素、β-胡萝卜素等成分调控AKT1、IL-6等靶点，干预脂质代谢、炎症及PI3K-AKT通路，抑制乳腺癌骨转移。 |
| 关键词: 乳腺癌骨转移 益气续骨合剂 网络药理学 分子对接 作用机制 |
| DOI： |
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| Mechanism of action of Yiqi Xugu mixture on bone metastasis of breast cancer: A study based on network pharmacology and molecular docking |
| LIU Jia,XU Jingxiao,YAO Shu |
| (Kunming Municipal Hospital of Traditional Chinese Medicine, Kunming 650051, Yunnan, China) |
| Abstract: |
| Objective: To investigate the mechanism of action of Yiqi Xugu mixture in the treatment of bone metastasis of breast cancer based on network pharmacology and molecular docking. Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and The Encyclopedia of Traditional Chinese Medicine were used to obtain the active components and targets of Yiqi Xugu mixture; The Cancer Genome Atlas was used to download the transcriptome data of breast cancer with bone metastasis, breast cancer without bone metastasis, and normal samples to identify differentially expressed genes （P < 0.01）; drug targets and disease targets were intersected to construct a drug-component-target network. The gene ontology functional annotation analysis and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed for key targets, the Protein-Protein Interaction （PPI） network was used to obtain hub genes, and molecular docking was used to verify binding activity. Results: A total of 254 drug targets, 12129 disease targets, and 181 intersecting targets were obtained. Enrichment analyses showed that the targets were involved in oxidative stress, inflammatory response, and the phosphoinositide 3-kinase/protein kinase B signaling pathway. The PPI network identified the hub genes of AKT Serine/Threonine Kinase 1 （AKT1）, Albumin （ALB）, Jun Proto-Oncogene （JUN）, interleukin- 6 （IL-6）, and Catenin Beta 1. Molecular docking confirmed that quercetin （binding to AKT1/JUN/IL-6） and β-carotene （binding to ALB） were the key active components （with a binding energy of <-3.42 kcal/mol）. Conclusion: Yiqi Xugu mixture may inhibit bone metastasis of breast cancer by regulating the targets such as AKT1 and IL-6 through the components including quercetin and β-carotene and intervening in lipid metabolism, inflammation, and the PI3K-AKT pathway. |
| Key words: bone metastasis of breast cancer Yiqi Xugu mixture network pharmacology molecular docking mechanism of action |
