Department of Central Laboratory, Clinical College of Lianyungang, Bengbu Medical University, Lianyungang, 222002, Jiangsu, China; Department of Central Laboratory, Lianyungang Hospital Affiliated to Kangda College of Nanjing Medical University, Lianyungang 222002, Jiangsu, China; Institute of Clinical Oncology, The Second People's Hospital of Lianyungang City (Cancer Hospital of Lianyungang), Lianyungang 222002, Jiangsu, China.
Department of Ultrasonography, The Second People's Hospital of Lianyungang City (Cancer Hospital of Lianyungang), Lianyungang 222002, Jiangsu, China.
J Ethnopharmacol. 2024 May 23;326:117912. doi: 10.1016/j.jep.2024.117912. Epub 2024 Feb 20.
Papillary thyroid carcinoma (PTC) is the predominant form of thyroid cancer with a rising global incidence. Despite favorable prognoses, a significant recurrence rate persists. Dioscorea bulbifera L. (DBL), a traditional Chinese medicine, has been historically used for thyroid-related disorders. However, its therapeutic effects and mechanisms of action on PTC remain unclear.
To explore the potential therapeutic effects, principal active components, and molecular mechanisms of DBL in the treatment of PTC through network pharmacology and molecular docking, with experimental validation conducted to corroborate these findings.
The Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) was utilized as a systematic tool for collecting and screening the phytochemical components of DBL, and for establishing associations between these components and molecular targets. Based on this, network data was visually processed using Cytoscape software (version 3.8.0). Concurrently, precise molecular docking studies of the principal active components of DBL and their corresponding targets were conducted using Autodock software. Additionally, PTC-related genes were selected through the GeneCards and GEO databases. We further employed the DAVID bioinformatics resources to conduct comprehensive Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on the intersecting genes between DBL and PTC. These analyses aid in predicting the potential therapeutic actions of DBL on PTC and its mechanisms of action. To validate these findings, corresponding in vitro experimental studies were also conducted.
In this investigation, 14 bioactive compounds of DBL and 195 corresponding molecular targets were identified, with 127 common targets shared between DBL and PTC. Molecular docking revealed strong binding affinities between major bioactive compounds and target proteins. GO enrichment analysis unveiled key processes involved in DBL's action. KEGG analysis highlighted DBL's modulation of the PI3K/AKT signaling pathway. Experimental outcomes demonstrated DBL's potential in inhibiting PTC cell proliferation and migration, suppressing PI3K/AKT pathway activation, and promoting ferroptosis.
In conclusion, DBL offers a multifaceted therapeutic approach for PTC, targeting multiple molecular entities and influencing diverse biological pathways. Network pharmacology and molecular docking shed light on DBL's potential utility in PTC treatment, substantiated by experimental validation. This study contributes valuable insights into using DBL as a promising therapeutic agent for PTC management.
甲状腺癌（PTC）是甲状腺癌的主要形式，其全球发病率呈上升趋势。尽管预后良好，但仍存在显著的复发率。薯蓣（DBL）是一种传统中药，历史上一直用于治疗与甲状腺有关的疾病。然而，其对 PTC 的治疗效果和作用机制尚不清楚。
通过网络药理学和分子对接探讨 DBL 治疗 PTC 的潜在治疗效果、主要活性成分和作用机制，并进行实验验证。
利用中药系统药理学数据库（TCMSP）作为系统工具，收集和筛选 DBL 的植物化学成分，并建立这些成分与分子靶标之间的关联。在此基础上，利用 Cytoscape 软件（版本 3.8.0）对网络数据进行可视化处理。同时，利用 Autodock 软件对 DBL 的主要活性成分及其相应靶点进行精确的分子对接研究。此外，通过 GeneCards 和 GEO 数据库选择 PTC 相关基因。我们还进一步利用 DAVID 生物信息学资源对 DBL 和 PTC 之间的交集基因进行全面的基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析。这些分析有助于预测 DBL 对 PTC 的潜在治疗作用及其作用机制。为了验证这些发现，还进行了相应的体外实验研究。
在本研究中，确定了 DBL 的 14 种生物活性化合物和 195 个相应的分子靶标，其中 DBL 和 PTC 之间有 127 个共同靶标。分子对接显示主要生物活性化合物与靶蛋白之间具有很强的结合亲和力。GO 富集分析揭示了 DBL 作用的关键过程。KEGG 分析突出了 DBL 对 PI3K/AKT 信号通路的调节作用。实验结果表明 DBL 具有抑制 PTC 细胞增殖和迁移、抑制 PI3K/AKT 通路激活和促进铁死亡的潜力。
综上所述，DBL 为 PTC 提供了一种多方面的治疗方法，针对多种分子实体并影响多种生物学途径。网络药理学和分子对接揭示了 DBL 在 PTC 治疗中的潜在应用，实验验证为其提供了支持。本研究为将 DBL 作为治疗 PTC 的有前途的治疗剂提供了有价值的见解。
