Academic Journal
Ginsenoside RD2 inhibits gastric cancer progression by suppressing TRIM46-mediated DUSP1 ubiquitination and modulating the ERK signaling pathway.
| Τίτλος: | Ginsenoside RD2 inhibits gastric cancer progression by suppressing TRIM46-mediated DUSP1 ubiquitination and modulating the ERK signaling pathway. |
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| Συγγραφείς: | Jiang J; Endoscopy Center, Minhang Hospital, Fudan University, No.170 Xinsong Road, Shanghai, 201199, China., Tang J; Endoscopy Center, Minhang Hospital, Fudan University, No.170 Xinsong Road, Shanghai, 201199, China., Li D; Endoscopy Center, Minhang Hospital, Fudan University, No.170 Xinsong Road, Shanghai, 201199, China., Qin Z; Endoscopy Center, Minhang Hospital, Fudan University, No.170 Xinsong Road, Shanghai, 201199, China., Li F; Endoscopy Center, Minhang Hospital, Fudan University, No.170 Xinsong Road, Shanghai, 201199, China., Bei S; Endoscopy Center, Minhang Hospital, Fudan University, No.170 Xinsong Road, Shanghai, 201199, China., Zhang X; Endoscopy Center, Minhang Hospital, Fudan University, No.170 Xinsong Road, Shanghai, 201199, China. Electronic address: zxh_njzx@163.com., Li H; Endoscopy Center, Minhang Hospital, Fudan University, No.170 Xinsong Road, Shanghai, 201199, China. Electronic address: 176545456@qq.com., Feng L; Endoscopy Center, Minhang Hospital, Fudan University, No.170 Xinsong Road, Shanghai, 201199, China. Electronic address: feng_li@fudan.edu.cn. |
| Πηγή: | Journal of pharmacological sciences [J Pharmacol Sci] 2026 Sep; Vol. 162 (1), pp. 11-28. Date of Electronic Publication: 2026 Jun 02. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Japanese Pharmacological Society Country of Publication: Japan NLM ID: 101167001 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1347-8648 (Electronic) Linking ISSN: 13478613 NLM ISO Abbreviation: J Pharmacol Sci Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Kyoto, Japan : Japanese Pharmacological Society, c2003- |
| Ιατρικοί όροι (MeSH): | Stomach Neoplasms*/pathology , Stomach Neoplasms*/genetics , Stomach Neoplasms*/drug therapy , Dual Specificity Phosphatase 1*/metabolism , Dual Specificity Phosphatase 1*/genetics , MAP Kinase Signaling System*/drug effects , MAP Kinase Signaling System*/genetics , Ginsenosides*/pharmacology , Ginsenosides*/therapeutic use , Ubiquitination*/drug effects , Ubiquitination*/genetics , Tripartite Motif Proteins*/metabolism , Phytotherapy*, Epithelial-Mesenchymal Transition/drug effects ; Epithelial-Mesenchymal Transition/genetics ; Cell Proliferation/drug effects ; Cell Proliferation/genetics ; Cell Movement/drug effects ; Gene Expression/drug effects ; Humans ; Cell Line, Tumor ; Disease Progression ; Animals ; Dose-Response Relationship, Drug |
| Περίληψη: | 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. (Copyright © 2026. Published by Elsevier B.V.) |
| Competing Interests: | Competing interests The authors have no conflicts of interest to declare. |
| Contributed Indexing: | Keywords: DUSP1; ERK signaling pathway; Gastric cancer; Ginsenoside RD2; TRIM46; Ubiquitination |
| Substance Nomenclature: | EC 3.1.3.48 (Dual Specificity Phosphatase 1) EC 3.1.3.48 (DUSP1 protein, human) 0 (Ginsenosides) 0 (Tripartite Motif Proteins) WB232T95AV (ginsenoside Rd) |
| Entry Date(s): | Date Created: 20260721 Date Completed: 20260721 Latest Revision: 20260721 |
| Update Code: | 20260722 |
| DOI: | 10.1016/j.jphs.2026.06.003 |
| PMID: | 42481127 |
| Βάση Δεδομένων: | MEDLINE |
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