Related Experiment Video
Updated: Oct 18, 2025
Establishment of Hepatocarcinoma in BALB/c-nu Mice and Investigation of the Therapeutic Effect of the Sanleng Jiashen Formula
Published on: January 26, 2024
Ginsenoside Rb1 Lessens Gastric Precancerous Lesions by Interfering With β-Catenin/TCF4 Interaction
Jinhao Zeng1,2, Xiao Ma3, Ziyi Zhao2
1Department of Chinese Internal Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Abstract:
Background: Seeking novel and effective therapies for gastric precancerous lesions (GPL) is crucial to reducing the incidence of gastric cancer. Ginsenoside Rb1 (GRb1) is a major ginsenoside in ginseng and has been proved to possess multiple bioactivities. However, whether GRb1 could protect against GPL and the underlying mechanisms have not been explored. Methods: We evaluated the effects of GRb1 on gastric precancerous lesions in rats on macroscopic, microscopic and ultramicroscopic levels. Then, an antibody array was employed to screen differential expression proteins (DEPs). Validation for the targeting DEP and investigation for the possible mechanism was conducted using immunohistochemistry, qRT-PCR, TUNEL apoptosis assay, immunoprecipitation and immunoblotting. Results: GRb1 was found to reverse intestinal metaplasia and a portion of dysplasia in the MNNG-induced GPL rats. The antibody array assay revealed seven DEPs in GPL rats as compared to control rats (5 DEPs were up-regulated, while two DEPs were down-regulated). Among the DEPs, β-catenin, beta-NGF and FSTL1 were significantly down-regulated after GRb1 administration. Our validation results revealed that enhanced protein expression and nuclear translocation of β-catenin were present in animal GPL samples. In addition, analysis of human gastric specimens demonstrated that β-catenin up-regulation and nuclear translocation were significantly associated with advanced GPL pathology. GRb1 intervention not only decreased protein expression and nuclear translocation of β-catenin, but interfered with β-catenin/TCF4 interaction. Along with this, declined transcriptional and protein expression levels of downstream target genes including c-myc, cyclin D1 and Birc5 were observed in GRb1-treated GPL rats. Conclusion: GRb1 is capable of preventing the occurrence and progression of GPL, which might be contributed by diminishing protein expression and nuclear translocation of β-catenin and interfering with β-catenin/TCF4 interaction.
Insights
Ginsenoside Rb1 (GRb1) prevents gastric precancerous lesions by reducing beta-catenin signaling. This natural compound offers a potential therapeutic strategy for gastric cancer prevention.
Area of Science:
- Gastroenterology and Oncology
- Pharmacology and Natural Products
Background:
- Gastric precancerous lesions (GPL) increase gastric cancer risk, necessitating novel therapeutic strategies.
- Ginsenoside Rb1 (GRb1), a key component of ginseng, exhibits diverse bioactivities but its role in GPL remains unexplored.
Purpose of the Study:
- To investigate the protective effects of GRb1 against gastric precancerous lesions in a rat model.
- To elucidate the underlying molecular mechanisms, particularly focusing on beta-catenin signaling.
Main Methods:
- GRb1 treatment efficacy assessed macroscopically, microscopically, and ultramicroscopically in MNNG-induced GPL rats.
- Differential protein expression screened using antibody arrays; key proteins validated via immunohistochemistry, qRT-PCR, and apoptosis assays.
- Beta-catenin/TCF4 interaction and downstream gene expression analyzed using immunoprecipitation and immunoblotting.
Main Results:
- GRb1 reversed intestinal metaplasia and dysplasia in GPL rats.
- GRb1 administration down-regulated beta-catenin, beta-NGF, and FSTL1.
- GRb1 decreased beta-catenin protein expression, nuclear translocation, and interfered with beta-catenin/TCF4 interaction, reducing c-myc, cyclin D1, and Birc5 levels.
Conclusions:
- GRb1 demonstrates potential in preventing the occurrence and progression of gastric precancerous lesions.
- The therapeutic effect of GRb1 is attributed to the inhibition of beta-catenin signaling pathway.
- GRb1 represents a promising natural compound for gastric cancer chemoprevention.
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:23Abnormal Proliferation
01:24Small GTPases - Ras and Rho
Three regulatory proteins control their activity: