Metformin inhibits early stage diethylnitrosamine-induced hepatocarcinogenesis in rats

Autor: Woo-Chan Son, Hyun‑Ji Choi, Ja June Jang, Eun Sil Yu, Minsun Chang, Woori Jo, Hyun-Kyu Park, Hyo‑Ju Lee, Jae‑Eun Ryu, Sungwoong Jang
Rok vydání: 2015
Předmět:
Male
0301 basic medicine
Cancer Research
Cirrhosis
endocrine system diseases
Carcinogenesis
Biochemistry
0302 clinical medicine
rat
Glutathione Transferase
Liver Neoplasms
Articles
hepatocellular carcinoma
Organ Size
Immunohistochemistry
Metformin
Liver
Oncology
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Molecular Medicine
Signal Transduction
medicine.drug
medicine.medical_specialty
Carcinoma
Hepatocellular
diethylnitrosamine
Blotting
Western
Biology
03 medical and health sciences
Proliferating Cell Nuclear Antigen
Internal medicine
Genetics
medicine
Carcinoma
Animals
Rats
Wistar
Molecular Biology
Neoplasm Staging
AMP-activated protein kinase
Oncogene
Adenylate Kinase
Body Weight
nutritional and metabolic diseases
Cancer
Hepatocellular adenoma
medicine.disease
Molecular medicine
digestive system diseases
030104 developmental biology
Endocrinology
Cancer research
Zdroj: Molecular Medicine Reports
ISSN: 1791-3004
1791-2997
DOI: 10.3892/mmr.2015.4513
Popis: 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.
Databáze: OpenAIRE
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