ArticleMolecular medicine reports2016
Metformin inhibits early stage diethylnitrosamine‑induced hepatocarcinogenesis in rats.
Article in Molecular medicine reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Constitutive AMPK activation prevents hepatocellular carcinoma development through inhibition of HNF4α activity.Science advances · 2026Article
- Therapeutic efficacy of canagliflozin against hepatocarcinogenesis induced by CDD/DEN/TAA in a rat model: regulation of AMPK/HIF-1α/YAP-1/TAZ signaling pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Mechanistic Insights about Sorafenib-, Valproic Acid- and Metformin-Induced Cell Death in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Review
- Drug repurposing: Metformin's effect against liver tissue damage in diabetes and prostate cancer model.Journal of diabetes and metabolic disorders · 2023Article
- Dairy consumption and hepatocellular carcinoma risk.Annals of translational medicine · 2021Review
- The Apoptotic Effect of Trichinella spiralis Infection Against Experimentally Induced Hepatocellular Carcinoma.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Metformin Improves Biochemical and Pathophysiological Changes in Hepatocellular Carcinoma with Pre-Existed Diabetes Mellitus Rats.Pathogens (Basel, Switzerland) · 2021Article
- Survival advantage associated with metformin usage in hepatocellular carcinoma patients with diabetes mellitus receiving radical resection: a propensity score matching analysis.European journal of gastroenterology & hepatology · 2020Article
- Animal Models of Hepatocellular Carcinoma Prevention.Cancers · 2019Review
- The Role of AMP-Activated Protein Kinase as a Potential Target of Treatment of Hepatocellular Carcinoma.Cancers · 2019Review
- Targeting AMPK, mTOR and β-Catenin by Combined Metformin and Aspirin Therapy in HCC: An Appraisal in Egyptian HCC Patients.Molecular diagnosis & therapy · 2018Article
- Gene expression, regulation of DEN and HBx induced HCC mice models and comparisons of tumor, para-tumor and normal tissues.BMC cancer · 2017Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antitumor effects of metformin have recently emerged despite its original use for type II diabetes. In the present study, the effects of metformin on the development and recurrence of hepatocellular carcinoma (HCC) were investigated using the diethylnitrosamine (DEN)‑induced rat model of HCC. Tumor foci were characterized by gross examination and by histopathological characteristics, including proliferation, hepatic progenitor cell content and the expression of hepatocarcinoma‑specific molecular markers. Potential target molecules of metformin were investigated to determine the molecular mechanism underlying the inhibitory effects of metformin on chemically induced liver tumorigenesis. The antitumor effects of metformin were increased by the reduction of surface nodules and decreased the incidence of altered hepatocellular foci, hepatocellular adenoma and carcinoma. Also, decreased expression levels of glutathione S‑transferase placental form, proliferating cell nuclear antigen and cytokeratin 8 described the inhibitory effects of metformin on HCC. In the present study, Wistar rats receiving treatment with DEN were administered metformin for 16 weeks. In addition, metformin suppressed liver tumorigenesis via an AMPK‑dependent pathway. These results suggested that metformin has promising effects on the early stage of HCC in rats. Therefore, metformin may be used for the prevention of HCC recurrence following primary chemotherapy for HCC and/or for high‑risk patients, including chronic hepatitis and cirrhosis.
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