ArticlePhytotherapy research : PTR2021
Resveratrol inhibits bile acid-induced gastric intestinal metaplasia via the PI3K/AKT/p-FoxO4 signalling pathway.
Article in Phytotherapy research : PTR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Stomach at the crossroads: nuclear receptor signaling at the interface between what we are and what we eat.Physiological reviews · 2026Review
- 17-β-Estradiol Protects Chondrocytes From Senescence and Ameliorates Osteoarthritis Progression via ERα-AKT-FOXO4 Pathway.Journal of cellular and molecular medicine · 2026Article
- CaSR regulates SLC26A6 expression via the PKA-FOXO4 signaling axis to promote experimental calcium oxalate kidney stone formation in rats.Frontiers in cell and developmental biology · 2026Article
- Long non-coding RNA PVT1 mediates bile acid-induced gastric intestinal metaplasia via a miR-34b-5p/HNF4α positive feedback loop.Chinese medical journal · 2025Article
- Modulation of the PI3K/Akt signaling pathway by resveratrol in cancer: molecular mechanisms and therapeutic opportunity.Discover oncology · 2025Review
- Molecular Alterations in Gastric Intestinal Metaplasia Shed Light on Alteration of Methionine Metabolism: Insight into New Diagnostic and Treatment Approaches.Biomedicines · 2025Review
- Article
- Natural products based on Correa's cascade for the treatment of gastric cancer trilogy: Current status and future perspective.Journal of pharmaceutical analysis · 2025Review
- Research progress on the therapeutic effects of effective components of traditional Chinese medicine in the treatment of gastric cancer precursors through modulation of multiple signaling pathways.Frontiers in oncology · 2025Review
- Crosstalk between bile acids and gut microbiota: a potential target for precancerous lesions of gastric cancer.Frontiers in pharmacology · 2025Review
- Article
- FOLR2Journal of experimental & clinical cancer research : CR · 2024Article
- Weiwei Decoction alleviates gastric intestinal metaplasia through the olfactomedin 4/nucleotide-binding oligomerization domain 1/caudal-type homeobox gene 2 signaling pathway.World journal of gastrointestinal oncology · 2024Article
- Antitumor Effects of Resveratrol Opposing Mechanisms ofNutrients · 2024Review
- GATA4 Forms a Positive Feedback Loop with CDX2 to Transactivate MUC2 in Bile Acids-Induced Gastric Intestinal Metaplasia.Gut and liver · 2024Article
- Article
- Exploration of gastric carcinogenesis from the relationship between bile acids and intestinal metaplasia and intragastric microorganisms (H. pylori and non-H. pylori).Journal of cancer research and clinical oncology · 2023Review
- mTORC2 orchestrates monocytic and granulocytic lineage commitment by an ATF5-mediated pathway.iScience · 2023Article
- The role of bile acid in intestinal metaplasia.Frontiers in physiology · 2023Review
- Resveratrol in breast cancer treatment: from cellular effects to molecular mechanisms of action.Cellular and molecular life sciences : CMLS · 2022Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Gastric intestinal metaplasia (GIM) is the essential pre-malignancy of gastric cancer. Chronic inflammation and bile acid reflux are major contributing factors. As an intestinal development transcription factor, caudal-related homeobox 2 (CDX2) is key in GIM. Resveratrol has potential chemopreventive and anti-tumour effects. The aim of the study is to probe the effect of resveratrol in bile acid-induced GIM. We demonstrated that resveratrol could reduce CDX2 expression in a time- and dose-dependent manner in gastric cell lines. A Cignal Finder 45-Pathway Reporter Array and TranSignal Protein/DNA Array Kit verified that resveratrol could increase Forkhead box O4 (FoxO4) activity and that Chenodeoxycholic acid (CDCA) could reduce FoxO4 activity. Furthermore, bioinformatics analysis showed that FoxO4 could bind to the CDX2 promoter, and these conjectures were supported by chromatin-immunoprecipitation (ChIP) assays. Resveratrol can activate FoxO4 and decrease CDX2 expression by increasing phospho-FoxO4 nucleus trans-location. Resveratrol could increase FoxO4 phosphorylation through the PI3K/AKT pathway. Ectopic FoxO4 expression can up-regulate FoxO4 phosphorylation and suppress CDCA-induced GIM marker expression. Finally, we found a reverse correlation between p-FoxO4 and CDX2 in tissue arrays. This study validates that resveratrol could reduce bile acid-induced GIM through the PI3K/AKT/p-FoxO4 signalling pathway and has a potential reversing effect on GIM, especially that caused by bile acid reflux.
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Registered trials
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