Expression and correlation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor and microvessel...

An experimental rat hepatocellular carcinoma (HCC) model was established using diethylnitrosamine and N-nitrosomorpholine to induce carcinogenesis in Sprague-Dawley rats. During hepatocarcinogenesis, seven rats were sacrificed at 0, 4, 8, 12 and 16 weeks and 10 rats were sacrificed at 20 weeks. The levels of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) protein and mRNA were examined by immunohistochemistry, Western blot and semi-quantitative reverse transcriptase-polymerase chain reaction at different stages in the rat HCC model. Twenty weeks after induction of hepatocarcinogenesis, the expression of HIF-1alpha and VEGF protein and mRNA significantly increased compared with week 0. Microvessel density (MVD) increased considerably once liver cancer developed. There was a significant positive correlation between MVD and both HIF-1alpha and VEGF, and between HIF-1alpha and VEGF levels. These results suggest that HIF-1alpha and VEGF play important roles in tumour occurrence and development during rat hepatocarcinogenesis, possibly through promoting tumour angiogenesis.