Journal of Pure and Applied MicrobiologyVol. 7 No. Special Edition

Dynamic Expression and Alteration of Vascular Endothelial Growth Factor and Angiopoietin in Hepatocyte Malignant Transformation and Hepatocarcinogenesis

Liwei Qiu1, Min Yao2, Haijian Zhang1, Meijuan Yan2, Li Wang2 and Dengfu Yao1*

1Research Center of Clinical Medicine, Affiliated Hospital of Nantong University and 2Medical School of Nantong University, Nantong 226001, Jiangsu Province, China.

Received on 03 March 2013 and accepted on 14 April 2013

 

ABSTRACT

To investigate the dynamic expression of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), and antiangiogenic therapy on hepatocyte malignant transformation. Hepatoma models were induced with 2-fluorenylacetamide (2-FAA) on male Sprague-Dawly rats, thalidomide was administered intragastrically (100 mg/kg body weight) to intervence HCC progress. VEGF expression was analyzed by immunohistochemistry, and its level was quantitatively detected by enzyme linked immunosorbent assay or by Western blotting. An increasing tendency of VEGF or Ang expressions in the 2-FAA group was found from hepatocyte denatured, precancerous, and cancerous stages confirmed by HE staining with highest values in the HCC group than those in controls (P<0.001). The positive relationship was closely found between VEGF and Ang level (P<0.01) with abnormality at the early stage. Interestingly, the morphologic changes of hepatocytes in the thalidomide group generated only punctiform denaturation or slightly necrosis at the early or middle stages, and nodular hyperplasia or a little atypical hyperplasia at the final stages, with the down-regulation of VEGF (2=8.024, P<0.001) and Ang (2=9.93, P<0.001) comparative with those in the 2-FAA group.The over-expressions of VEGF and Ang-2 are associated with hepatocyte malignant transformation, and antiangiogenic treatment can down-regulate the both expression and delay hepatoma formation.

Keywords : Hepatocellular carcinoma, Rat hepatoma model, Vascular endothelial growth factor, Angiopoietin-2, Immunohistochemistry, Dynamic expression.