Background/aims: Hepatocellular carcinoma (HCC) is hypervascular. Pigment epithelial derived factor (PEDF), a potent angiogenic inhibitor, usually coexists with the stimulator, vascular endothelial growth factor (VEGF). To assess the treatment effect of PEDF on growing HCCs we conducted this study.
Methodology: Pathogen-free male LEW/SsN rats (n=150 in 5 groups), group A as control, groups B, C, D and E were given diethyl nitrosamine (DEN) to induce HCC. Group C received intraperitoneal injection (i.p.) of PEDF (0.3mg/kg/day) since induction. Group D received i.p. of PEDF (0.3mg/kg/day) since 18th week (wk). Group E received i.p. of normal saline. We examined VEGF mRNA and PEDF mRNA of livers of group A and 3 different areas (advancing edge, inner edge and central area) of HCC of other 4 groups at 24th wk.
Results: Tumor weight and metastasis score of group C were significantly lower (p=0.026). Comparing among 5 groups, the ratio of VEGF/PEDF mRNA of inner edge of HCC of group C and D were significantly lower (p=0.002 and p=0.011). By multivariate analysis, the difference of group C remains significant (p=0.030).
Conclusions: PEDF significantly suppresses rat hepatocarcinogenesis if given simultaneously since cancer induction. The significant decrease of VEGF/PEDF mRNA is at the inner edge of HCC.