Effects of mutant p27 gene on angiogenesis of hepatocellular carcinoma in nude mice

Abstract

Objective To observe the effects of mutant p27 (p27mt) gene on the angiogenesis of SMMC-7721 cells in nude mice.Methods A mouse model of human hepatocellular carcinoma (SMMC-7721 cell line) was established by subcutaneous transplantation in BALB/c mice.The 30 mice were then divided into three groups,which were injected with PBS,Ad-LacZ and Ad-p27mt respectively,and the angiogenesis of the transplanted liver tumor was observed.The expression of p27 was detected by Western blotting,the expression levelss of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 were immunohistochemically determined,and Ⅷ factor was examined through immunofluorescence.Results As compared with blank control and the Ad-Lac-Z groups,p27 protein expression in Ad-p27mt group was obviously increased,but the expression of VEGF and MMP-9 in Ad-p27mt group was significantly decreased (P ＜0.05).The average absorbence (AA) of Ⅷ factor in Ad-p27 group was 0.201 ±0.103,and that in the blank control and the Ad-Lac-Z groups was 0.346 ± 0.069 and 0.351 ± 0.045 respectiyely,with difference being significant between the former and the latter.Conclusion p27mt could express p27 protein in hepatocellular carcinoma,and the p27 protein could significantly inhibit the angiogenesis of tumor through down-regulating the expression of VEGF and MMP-9. Key words: Mutant p27 gene; Angiogenesis; Carcinoma, hepatocellular