Molecular mechanism of Gancao Xiexin Decoction regulating EMT and suppressing hepatic metastasis of gastric cancer via the TGF-β1/SMAD pathway

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.