Biochemical/metabolic changes associated with hepatocellular carcinoma development in mice.

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality after lung and stomach cancers. This work was undertaken to investigate some of the biochemical mediators/pathways associated with or implicated in the pathogenesis of HCC. Male albino mice were classified into two groups: normal control group and HCC group. Early stage HCC was induced by injection of diethylnitrosamine (DEN) i.p. 200 mg/kg as a single dose, and after 2 weeks, the mice were given i.p. injection of thioacetamide (TAA) 100 mg/kg twice per week for 4 weeks. Mice were left for further 2 weeks without any treatment, after which, mice were sacrificed; blood and liver samples were collected. Serum was used for determination of activities of glucose-6-phosphate dehydrogenase (G6PDH) and aldolase as well as levels of insulin-like growth factor-1 (IGF-1) and epithelial cadherin (E-cadherin). One portion of the liver was used for histopathological examination and immunohistochemical staining of the tumor suppressor p53 protein. Another portion of the liver was used for determination of citrate synthase activity. Induction of HCC in mice resulted in significant increase in G6PDH and aldolase activities, and E-cadherin level, but significant decrease in IGF-1. HCC mice group showed moderate expression of p53 protein. These results suggest that the molecular pathogenesis of HCC in mice involves reduction of serum level of IGF-1 and increased serum level of E-cadherin accompanied by dysregulation of p53 protein expression. HCC was also associated with reprogrammed metabolic profile shifted toward increased glycolysis and lipogenesis.