Guo Huina, Lou Yichen, Hou Xiaofang, Guan Xiaoya, Guo Yujia, Han Qi, Xue Xuting, Wang Ying, He Long, Li Zhongxun, Zhang Chunming
Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, China.
Shanxi Province Clinical Medical Research Center for Precision Medicine of Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, China.
Front Pharmacol. 2025 Apr 25;16:1542116. doi: 10.3389/fphar.2025.1542116. eCollection 2025.
Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of the head and neck, with poor prognosis for advanced patients, and there is an urgent need to find new treatment strategies. Codonopsis pilosula, a traditional Chinese medicinal herb, possesses various pharmacological activities, but its antitumor effects and mechanisms in LSCC are still unclear. The aim of this study was to systematically investigate the potential antitumor mechanism of Codonopsis pilosula in LSCC.
In this study, we screened the effective compounds and targets of Codonopsis pilosula by TCMSP, ETCM and BATMAN-TCM databases, and screened targets related to LSCC by combining DisGeNET, GeneCards database and Cytoscape software. KEGG pathway enrichment analysis was utilized to explore the related signaling pathways. The core targets were further screened based on TCGA and GEO database analysis, and molecular docking was carried out to predict their binding ability to effective compounds. The presence of key compounds was verified by LC-MS, the MAPK3 expression was detected by qPCR in LSCC tissues, and the effects of MAPK3 knockdown on proliferation, migration, invasion, cell cycle, and apoptosis of LSCC cells were evaluated by cellular function assays.
In this study, 22 targets of Codonopsis pilosula that might regulate LSCC were screened based on network pharmacology. KEGG pathway enrichment analysis showed that Codonopsis pilosula-LSCC targets were mainly involved in HIF-1, TNF, IL-17 and FoxO signaling pathways. Based on TCGA and GEO database analysis, MAPK3 was identified as the core target of Codonopsis pilosula-LSCC. The molecular docking results showed that a variety of effective compounds from Codonopsis pilosula had strong binding abilities to MAPK3, among them, Caprylic Acid, Emodin and Luteolin have been confirmed by LC-MS. QPCR analysis indicated that MAPK3 was highly expressed in LSCC tissues. MAPK3 knockdown significantly inhibits LSCC cell proliferation, migration and invasion. It also suppresses LSCC cell growth by blocking the cell cycle and inducing apoptosis.
Codonopsis pilosula exerts antitumor effects in LSCC through the regulation of MAPK3 and multiple signaling pathways, providing a theoretical basis for its clinical application.
喉鳞状细胞癌（LSCC）是头颈部常见的恶性肿瘤，晚期患者预后较差，迫切需要寻找新的治疗策略。党参是一种传统中药材，具有多种药理活性，但其在LSCC中的抗肿瘤作用及机制尚不清楚。本研究旨在系统探讨党参在LSCC中的潜在抗肿瘤机制。
本研究通过TCMSP、ETCM和BATMAN-TCM数据库筛选党参的有效化合物和靶点，并结合DisGeNET、GeneCards数据库和Cytoscape软件筛选与LSCC相关的靶点。利用KEGG通路富集分析探索相关信号通路。基于TCGA和GEO数据库分析进一步筛选核心靶点，并进行分子对接以预测其与有效化合物的结合能力。通过LC-MS验证关键化合物的存在，用qPCR检测LSCC组织中MAPK3的表达，并通过细胞功能实验评估MAPK3敲低对LSCC细胞增殖、迁移、侵袭、细胞周期和凋亡的影响。
本研究基于网络药理学筛选出22个可能调控LSCC的党参靶点。KEGG通路富集分析表明，党参-LSCC靶点主要参与HIF-1、TNF、IL-17和FoxO信号通路。基于TCGA和GEO数据库分析，MAPK3被确定为党参-LSCC的核心靶点。分子对接结果表明，党参的多种有效化合物与MAPK3具有较强的结合能力，其中辛酸、大黄素和木犀草素已通过LC-MS得到证实。QPCR分析表明，MAPK3在LSCC组织中高表达。MAPK3敲低显著抑制LSCC细胞的增殖、迁移和侵袭。它还通过阻断细胞周期和诱导凋亡来抑制LSCC细胞生长。
党参通过调控MAPK3和多条信号通路在LSCC中发挥抗肿瘤作用，为其临床应用提供了理论依据。
