Liu Ming, Zheng Li, Zhang Yang, Tian Jinhui
Evidence-based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou City, No.199 Donggang West Road, 730000, Gansu Province, China.
Department of Pharmacy, China Aerospace Science & Industry Corporation 731 Hospital, Beijing, China.
Sci Rep. 2025 Jan 22;15(1):2856. doi: 10.1038/s41598-025-87286-z.
Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors, and lack of human epidermal growth factor receptor 2 (HER2) expression. Traditional Chinese medicine (TCM) has demonstrated promising efficacy in treating TNBC. This study explored the mechanisms of pachymic acid (PA) on TNBC by merging network pharmacology with experimental validation. We acquired Microarray data of TNBC from the Gene Expression Omnibus (GEO). The related targets of PA were predicted and screened using the following 6 databases: Swiss Target Prediction, HERB (Herbal Medicine Database), ETCM (Encyclopedia of Traditional Chinese Medicine), BATMAN (Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine), HIT (Herb Ingredients' Targets Database), and PharmMapper. The STRING interaction network analysis tool was used to create Protein-Protein Interaction (PPI) networks. Enrichment analysis included Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We conducted a pan-cancer analysis, tumor immune microenvironment analysis, and molecular docking. We performed cell experimental, included cytotoxicity assay, apoptosis analysis, proliferation assay, and migration and invasion assays. PA has potential for treating TNBC with the target of TOP2A, and platinum drug resistance possibly serving as the KEGG pathway through which PA exerts its therapeutic effects. PA is involved in processes such as nuclear division, chromosome segregation, mitotic nuclear division, condensed chromosome formation, and protein C-terminus binding. PA probably exert its therapeutic effects through the tumor immune microenvironment, involving elements such as Dendritic cells activated, Eosinophils, Macrophages M0, Macrophages M1, and T cells CD4 memory activated. The therapeutic effects of PA may vary across different subtypes of TNBC such as TNBC-BL1, TNBC-Metaplastic, and TNBC-BL2. This study provides compelling evidence that PA holds significant promise as a therapeutic agent for TNBC, primarily through its action on TOP2A and its influence on the TNBC.
三阴性乳腺癌（TNBC）的特征是缺乏雌激素和孕激素受体，且人表皮生长因子受体2（HER2）不表达。中医在治疗TNBC方面已显示出有前景的疗效。本研究通过将网络药理学与实验验证相结合，探索了茯苓酸（PA）对TNBC的作用机制。我们从基因表达综合数据库（GEO）获取了TNBC的微阵列数据。使用以下6个数据库预测并筛选PA的相关靶点：瑞士靶点预测数据库、HERB（草药数据库）、ETCM（中医百科全书）、BATMAN（中药分子机制生物信息学分析工具）、HIT（草药成分靶点数据库）和PharmMapper。使用STRING相互作用网络分析工具创建蛋白质-蛋白质相互作用（PPI）网络。富集分析包括基因本体论（GO）和京都基因与基因组百科全书（KEGG）。我们进行了泛癌分析、肿瘤免疫微环境分析和分子对接。我们进行了细胞实验，包括细胞毒性测定、凋亡分析、增殖测定以及迁移和侵袭测定。PA以TOP2A为靶点治疗TNBC具有潜力，铂类耐药可能是PA发挥治疗作用的KEGG途径。PA参与核分裂、染色体分离、有丝分裂核分裂、浓缩染色体形成和蛋白质C末端结合等过程。PA可能通过肿瘤免疫微环境发挥其治疗作用，涉及激活的树突状细胞、嗜酸性粒细胞、M0巨噬细胞、M1巨噬细胞和活化的CD4记忆T细胞等因素。PA的治疗效果在TNBC的不同亚型如TNBC-BL1、TNBC-化生型和TNBC-BL2中可能有所不同。本研究提供了有力证据，表明PA作为TNBC的治疗药物具有巨大潜力，主要通过其对TOP2A的作用及其对TNBC的影响。
