Abstract: Objective To investigate the expression of zinc-α2-glycoprotein (AZGP1) in a rat model of hepatocellular carcinoma (HCC), and its relationship with HCC progression.Methods Cirrhosis and HCC in rat models were established by diethylnitrosamine (DEN) water feeding, and subcutaneous tumor and orthotopic liver transplantation models in nude mice were constructed by injection of HepG2 cells with AZGP1 gene over-expressed interferenced vector. The expressions of AZGP1 and transforming growth factor β1 (TGFβ1) were detected by immunohistochemistry staining, westernblot (WB) and polymerase chain reaction (PCR), respectively, then the relationship among AZGP1, tumor size and metastasis rate was evaluated. Results The level of AZGP1 mRNA (0.20±0.02, p=0.003) was lower in HCC tissues than that in normal or cirrhosis tissues. Hepatic expression of AZGP1 proteins was absent or low-expressed, which was confirmed by quantitative immunohistochemical and WB analysis. Hepatic TGFβ1 gene and protein in cirrhotic and HCC tissues were significantly increased. The size of subcutaneous tumors had no difference between AZGP1 over-expressed HepG2 cells treated group (HepG2-AZGP1 group) and the control group (HepG2-GFP group). The incidence of lung metastasis was 57% in HepG2-AZGP1 group and 14% in HepG2-GFP group at week 6 after transplantation of subcutaneous tumors in nude mice. Compared with those in HepG2-GFP group, the numbers and sizes of tumor nodules in liver and lung were significantly decreased and the distinct atypia degrees of cancer cells were significantly lower in HepG2-AZGP1 group.Conclusion During the progression from cirrhosis to HCC, AZGP1 loss occurred accompanied with derepression of TGFβ1, which was proposed that function recovery of AZGP1 might be a new promising approach to reversing HCC.

Key words: Hepatocellular carcinoma (HCC), Zinc-α2-glycoprotein 1 (AZGP1), Transforming growth factor-β1 (TGF-β1), Cirrhosis