Ginsenoside Rh7 affects β-catenin nuclear translocation by inhibiting SHCBP1 expression, thereby inhibiting epithelial-mesenchymal transition in gastric cancer cells.

Background

Ginsenoside Rh7 is a bioactive compound with anticancer properties. This investigation was conducted to analyze the anticancer effects of ginsenoside Rh7 and its underlying molecular mechanisms in gastric cancer (GC) cells.

Methods

The key gene module associated with GC was identified through weighted gene co-expression network analysis (WGCNA) of the GSE118897 dataset. Differentially expressed genes (DEGs) were examined in The Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD) and the GSE118897 datasets. The central genes of this study were subsequently identified by intersection analysis and protein-protein interaction (PPI) network. Transcriptome sequencing evaluated the changes in SHCBP1 expression in GC cells treated with Rh7. Immunoprecipitation (IP) was employed to analyze the relationship between β-catenin and SHCBP1. Functional assays, including Transwell, cell counting kit-8 (CCK-8), colony assays, and in vivo tumor models, evaluated the effects of Rh7 and SHCBP1 on GC cell behaviors.

Results

SHCBP1 was upregulated in tumor samples in GSE118897 and TCGA-STAD. Ginsenoside Rh7 inhibited GC cell invasion, migration, and proliferation dose-dependently by downregulating SHCBP1 expression. Transcriptome analysis confirmed Rh7-mediated SHCBP1 inhibition. Rh7 promoted β-catenin nuclear translocation by reducing SHCBP1 expression. Rescue experiments demonstrated that the overexpression of SHCBP1 partially counterbalanced the impacts of Rh7 on epithelial-mesenchymal transition (EMT) regulation and GC cell growth in vitro and in vivo.

Conclusion

Ginsenoside Rh7 suppresses GC progression by regulating SHCBP1-mediated β-catenin nuclear translocation, thereby inhibiting EMT, proliferation, migration, and invasion. This highlights its potential as a GC therapeutic drug and deserves further study of its mechanism of action.