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.

TCA Cycle Rewiring as Emerging Metabolic Signature of Hepatocellular Carcinoma

“…CS presents either up-regulation or increased enzymatic activity in various cancer types such as ovarian and pancreatic cancer [67,68]. Noteworthy, CS enzyme activity has been reported to be increased in HCC [69]. More recently, RNAseq analysis-then verified in multiple microarray data sets-identified CS overexpression among unique 22-carbon-metabolism-gene signature of HCC [70].…”

Emerging Role of the Pentose Phosphate Pathway in Hepatocellular Carcinoma

“…Elevated G6PD activity, mRNA, and protein levels were also observed in rat preneoplastic nodules and HCC (75, 76) induced by the resistant-hepatocyte (R-H) protocol of carcinogenesis (77). Interestingly, a significant increase in serum G6PD activity has been recently seen in mice with HCC induced by DENA/thioacetamide (78). …”

The role of fibroblast growth factor 21 in the pathogenesis of liver disease: a novel predictor and therapeutic target

“…Furthermore, in vitro using luciferase reporter assays, p53 expression was able to downregulate FGF21 promoter activity via the cis-acting sequence in the proximal promoter of FGF21. Consequently, when dysregulation of p53 protein expression occurs, a large number of FGF21 is activated in liver tissues [60]. Recently, a study showed that PPAR-a participates in hepatocarcinogenesis [56].…”