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

Abstract

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.