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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.

Nonalcoholic fatty liver disease (NAFLD) can lead to cirrhosis, hepatocellular carcinoma, and ultimately death. Magnetic resonance techniques are accurate, noninvasive methods for evaluating hepatic steatosis but, in animals, have not been fully validated against histologic findings. We sought to validate the MRI fat-signal fraction (MRI-FSF) used for diagnosing NAFLD in human nonclinical trials by comparing MRI data with histopathologic findings in C57BL/6J mice (n = 24) fed normal chow (controls) or a methionine- and choline-deficient (MCD) diet to induce NAFLD. Axial T2-weighted fast spin-echo images were used to examine the entire liver. For histopathologic analyses, liver slides were evaluated for hepatic steatosis according to the NAFLD activity score. Pearson correlation coefficient and receiver operating characteristics analyses were performed. According to the fat-fraction signal, the mean percentage of liver fat in mice with induced NAFLD was 57%, which correlated with the histologically determined steatosis grade. The proton-density fat fraction effectively distinguished severe from mild hepatic steatosis, with an AUC of 0.92. Evaluation accuracy decreased when lobular inflammation and hepatocellular ballooning were considered. This study showed strong concurrence between MRI-FSF and histopathologic steatosis in a murine model of NAFLD. MRI-FSF had moderate sensitivity and specificity in this context. These results confirm that the MRI is a useful biomarker of hepatic steatosis in NAFLD in murine model.