الفهرس 
IntroductionOnly 14 pages are availabe for public view
Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common and dangerous type of liver cancer with high incidence. HCC increases the mortality rate despite the effectiveness of some chemotherapy and radiotherapy, due to chemotherapeutic resistance, toxicity, adverse effects and high cost.
AIM of the study: (1) To re-evaluate the anticarcinogenic effect of metformin in a cancer model not associated with diabetes.
(2) To evaluate the pharmacological anti-diabetic doses of metformin used in most cancer studies at early stages of HCC versus sub-pharmacological doses for possible use in oncology.
METHODS: HCC was induced by DEN/ CCl4 intraperitoneal injections to mice. The mice were treated by different doses of metformin. Morphological, biochemical, histological and immunohistochemical studies were done to examine metformin effect.
RESULTS: The low dose of metformin repressed HCC progression by significantly decreasing liver biomarkers, reducing the number and size of hepatic nodules, along with histological downstaging of HCC. This was achieved by the activation of Bax and suppressing BCL-2, VEGF, and PCNA. However, mice treated with metformin 250 mg/kg b.wt. showed increased mortality rate and signs of lactic acidosis, which was proven by significant increase in serum lactate dehydrogenase compared with HCC control group. This group also showed no significant difference in the number of nodules or the immunohistochemical markers compared to HCC group.
CONCLUSION: The results of this study concluded that the pharmacological dose of metformin cannot be used at advanced stages of HCC, while sub-pharmacological dose of metformin showed promising anticarcinogenic effect in chemically-induced hepatocellular carcinoma model not associated with diabetes.