Wenjing Liu , Doudou Lu , Shumin Jia , Yating Yang , Fandi Meng , Yuhua Du , Yi Yang , Ling Yuan , Yi Nan
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引用次数: 0
Abstract
Ethnopharmacological relevance
Gastric cancer (GC) is a highly malignant tumor of the digestive tract, posing a significant menace to human health. Gancao Xiexin Decoction (GCXXD), being a traditional Chinese medicine (TCM), has a good effect on inhibiting the proliferation and metastasis of GC. However, its mechanisms still need further investigation.
Aim of study
To investigate the mechanism by which GCXXD inhibits GC metastasis through network pharmacology, and to verify through in vivo and in vitro experiments.
Materials and methods
The TCMSP and GEO databases, in combination with UPLC-MS/MS techniques, were employed to identify the hub genes, active ingredients, and critical pathways of GCXXD in the treatment of GC. Subsequently, molecular docking was conducted on both the hub genes and the core components. Finally, based on the results of the bioinformatics analysis, the role of GCXXD in inhibiting liver metastasis of GC was elucidated through in vivo and in vitro experiments, including scratch assays, Transwell assays, HE staining, immunohistochemistry, in vivo live imaging, qRT-PCR, and Western blotting.
Results
Utilizing UPLC-MS/MS and network pharmacology, we identified 20 active ingredients and 5 hub targets in the treatment of GC by GCXXD. Through KEGG analyses, GCXXD treatment of GC could through the TGF-beta pathway. In vivo and in vitro experiments, GCXXD downregulated the mRNA and protein expression level of hub genes involved in the TGF-β1/SMAD pathway and the EMT process. Additionally, GCXXD significantly reduced the incidence of liver metastases in GC.
Conclusion
GCXXD inhibited EMT via blocking the TGF-β1/SMAD pathway, which suppressed GC cell growth and liver metastasis. This study provides data to support the treatment of liver metastasis in GC with TCM and holds significant importance for the research and development of new anticancer drugs.
期刊介绍：
The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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