Ginsenoside Rb1 Lessens Gastric Precancerous Lesions by Interfering With β-Catenin/TCF4 Interaction

Frontiers in Pharmacology

Junrong Yu¹  Yanwei Hao¹  Zhongzhen Zeng¹  Maoyuan Zhao¹  Nianzhi Chen¹  Daoyin Gong²  Xiao Ma³  Jianyuan Tang⁴  Jundong Wang⁴  Yu Chen⁴  Ziyi Zhao⁴  Jinhao Zeng⁴ 

[1] Department of Chinese Internal Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China;Department of Pathology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China;School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China;TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China;

关键词: ginsenoside Rb1;    gastric precancerous lesions;    intestinal metaplasia;    dysplasia;    β-catenin/TCF4 interaction;   

DOI  :  10.3389/fphar.2021.682713

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown