Background Ginsenoside RD2, a bioactive compound derived from ginseng, has been shown to possess various biological activities, including potential anti-cancer effects. However, its therapeutic efficacy and molecular mechanisms, particularly in gastric cancer (GC), remain inadequately understood. Methods The impact of RD2 on GC cells' malignant behavior, epithelial-mesenchymal transition (EMT), and tumor growth in vivo were analyzed in vitro and in vivo. Hub genes were identified using bioinformatics analysis of the Cancer Genome Atlas (TCGA)-Stomach Adenocarcinoma (STAD) dataset and RNA sequencing (RNA-Seq) analysis of AGS cells treated with 80 μM RD2. After treating cells with RD2, cell viability, colony formation, and transwell assays were carried out to assess the functions of TRIM46 and DUSP1 in mediating the effects of RD2. Results In a dose-dependent fashion, RD2 dramatically reduced the proliferation, migration, and invasion of GC cells. RD2 treatment reduced the expression of N-cadherin, Vimentin, and Snail and increased that of E-cadherin. Gene expression analysis showed that six key genes (MUC1, MMP9, COL18A1, GPC1, TRIM46, JUP) were downregulated by RD2. In addition, RD2 decreased TRIM46 expression and increased DUSP1 levels, suggesting a potential association with ERK signaling. TRIM46 overexpression reversed the inhibitory effect of RD2 on GC progression, while DUSP1 overexpression counteracted the effects of TRIM46 on EMT and cell viability. Conclusion Our results suggest RD2 inhibits GC progression through modulation of TRIM46 and DUSP1, with potential involvement of ERK signaling. TRIM46 promotes GC cell growth and EMT, while DUSP1 overexpression counteracts these effects, highlighting the potential therapeutic target of RD2 in GC treatment.
Jiang et al. (Mon,) studied this question.