Evaluation of Notch and Hypoxia Signaling Pathways in Chemically Induced Hepatocellular Carcinoma in Rats

Abstract

Hepatocellular carcinoma (HCC) is a common worldwide malignancy. Notch signaling pathway contributes to the genesis of diverse cancers, however, its role in HCC is unclear. Hypoxia is a common feature of HCC. Signal integration between Notch and hypoxia may be involved in HCC. The aim of this study was to evaluate the expression of some Notch pathway genes, in addition to hypoxia inducible factor-1 alpha (HIF-1α) during rat hepatocellular carcinogenesis. The study aimed also, to identify any crosstalk between Notch signaling and hypoxia throughout hepatocellular oncogenesis in rats. Hepatocellular carcinogenesis was chemically induced in rats. Tissue specimens were examined histopathologically and classified into early preneoplastic group, advanced preneoplastic group, and control group. The expression of Notch-1, Dll-4, and HIF-1α was evaluated in tissue samples by total RNA extraction and RT-PCR. The expression of target genes were significantly increased in the diseased groups than in control group. There was a significant correlation between the expression of Notch1, Dll-4, and HIF-1α. These results indicate that overexpression of Notch-1, Dll-4, and HIF-1α may be associated with the malignant transformation of hepatocytes with a possible Notch – hypoxia cross talk during hepatocellular oncogenecity.

Keywords: HCC; Notch1; Dll-4; HIF-1α; rats