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The mechanistic study of codonopsis pilosula on laryngeal squamous cell carcinoma based on network pharmacology and
Huina Guo1,2, Yichen Lou1,2,3, Xiaofang Hou1,2,3
1Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, First Hospital of Shanxi Medical University, Taiyuan, China.
Introduction:
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.
Methods:
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.
Results:
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.
Conclusion:
Codonopsis pilosula exerts antitumor effects in LSCC through the regulation of MAPK3 and multiple signaling pathways, providing a theoretical basis for its clinical application.
Insights
Codonopsis pilosula exhibits antitumor effects against laryngeal squamous cell carcinoma (LSCC) by regulating MAPK3. This traditional herb inhibits LSCC progression by impacting cell proliferation, migration, and apoptosis, offering a new therapeutic avenue.
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Laryngeal squamous cell carcinoma (LSCC) presents a poor prognosis for advanced cases, necessitating novel treatment strategies.
- Codonopsis pilosula, a traditional Chinese herb, has demonstrated various pharmacological activities, but its specific antitumor mechanisms in LSCC remain largely unexplored.
Purpose of the Study:
- To systematically investigate the potential antitumor mechanisms of Codonopsis pilosula in LSCC.
- To identify key compounds and molecular targets of Codonopsis pilosula relevant to LSCC treatment.
Main Methods:
- Network pharmacology was employed to screen compounds and targets of Codonopsis pilosula and LSCC.
- KEGG pathway enrichment analysis identified relevant signaling pathways.
- TCGA and GEO databases were used to identify core targets, followed by molecular docking and LC-MS validation.
- MAPK3 expression and functional effects of its knockdown were assessed in LSCC cells and tissues.
Main Results:
- Network pharmacology identified 22 potential targets, with MAPK3 emerging as a core target regulated by Codonopsis pilosula in LSCC.
- KEGG analysis revealed involvement in HIF-1, TNF, IL-17, and FoxO signaling pathways.
- Codonopsis pilosula compounds showed strong binding to MAPK3; Caprylic Acid, Emodin, and Luteolin were confirmed.
- High MAPK3 expression in LSCC was observed, and its knockdown inhibited proliferation, migration, invasion, and induced apoptosis, while blocking the cell cycle.
Conclusions:
- Codonopsis pilosula demonstrates significant antitumor effects in LSCC through the regulation of MAPK3 and associated signaling pathways.
- These findings provide a theoretical foundation for the potential clinical application of Codonopsis pilosula in treating LSCC.
