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Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma
Published on: July 25, 2011
Network pharmacology and experiment validation investigate the potential mechanism of triptolide in oral squamous
Puyu Hao1,2, Pengcheng Zhang2, Ying Liu2
1Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China.
Abstract:
Objective: This study aimed to investigate the molecular mechanism of triptolide in the treatment of oral squamous cell carcinoma (OSCC) via network pharmacology and experimental validation. Methods: The network pharmacological method was used to predict the key targets, detect the signal pathways for the treatment of OSCC, and screen the critical components and targets for molecular docking. Predicted targets were validated in cellular and xenograft mouse model. Results: In this study, we predicted action on 17 relevant targets of OSCC by network pharmacology. PPI network demonstrated that Jun, MAPK8, TP53, STAT3, VEGFA, IL2, CXCR4, PTGS2, IL4 might be the critical targets of triptolide in the treatment of OSCC. These potential targets are mainly closely related to JAK-STAT and MAPK signaling pathways. The analysis of molecular docking showed that triptolide has high affinity with Jun, MAPK8 and TP53. Triptolide can suppress the growth of OSCC cells and xenograft mice tumor, and downregulate the expression of Jun, MAPK8, TP53, STAT3, VEGFA, IL2, CXCR4, PTGS2 to achieve the therapeutic effect of OSCC. Conclusion: Through network pharmacological methods and experimental studies, we predicted and validated the potential targets and related pathways of triptolide for OSCC treatment. The results suggest that triptolide can inhibit the growth of OSCC via several key targets.
Insights
Triptolide effectively treats oral squamous cell carcinoma (OSCC) by targeting key molecules like Jun and MAPK8. This natural compound suppresses tumor growth through identified molecular mechanisms and signaling pathways.
Area of Science:
- Molecular biology
- Pharmacology
- Oncology
Background:
- Oral squamous cell carcinoma (OSCC) is a prevalent malignancy with limited treatment options.
- Understanding the molecular mechanisms of therapeutic agents is crucial for improving OSCC treatment outcomes.
Purpose of the Study:
- To investigate the molecular mechanisms of triptolide in treating OSCC using network pharmacology and experimental validation.
- To identify key targets and signaling pathways involved in triptolide's anti-cancer effects on OSCC.
Main Methods:
- Network pharmacology was employed to predict potential targets and pathways.
- Molecular docking was performed to assess the binding affinity of triptolide with predicted targets.
- In vitro (cell lines) and in vivo (xenograft mouse models) experiments were conducted for validation.
Main Results:
- Network pharmacology identified 17 potential targets for triptolide in OSCC treatment.
- Key targets including Jun, MAPK8, and TP53 showed high binding affinity with triptolide.
- Triptolide demonstrated significant suppression of OSCC cell and tumor growth, downregulating key target expressions.
Conclusions:
- Triptolide exhibits therapeutic potential for OSCC by inhibiting tumor growth through multiple key targets.
- The JAK-STAT and MAPK signaling pathways are implicated in triptolide's mechanism of action against OSCC.
- Combined network pharmacology and experimental validation provide a robust approach to understanding triptolide's efficacy in OSCC.
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