bFGF Up-regulation Reduces Spontaneous Necrosis of VX2 Tumors Without Increasing Tumoral Microvascular Density

Abstract

Aim: To determine whether up-regulation of basic fibroblast growth factor (bFGF) in VX2 cells reduces tumor necrosis.

Materials and methods: VX2 cells were transfected with expression vector containing cDNA of rabbit bFGF. Stable clones producing rabbit bFGF (bFGF-VX2) were selected. bFGF-VX2 (n=5) or non-transfected VX2 (control) (n=5) cells were implanted into leg muscle of 10 rabbits. The tumors were characterized 21 days after grafting.

Results: Overexpression of bFGF by VX2 tumors significantly reduced necrosis (p<0.0223) and increased cell viability (p<0.0223), without effect on the mean vascular density. bFGF concentration was significantly higher in bFGF-VX2 tumors (p<0.0062) and negatively correlated with tumor volume at day 21 (ρ=-0.927, p<0.0034). Vascular endothelial growth factor concentration was significantly lower in bFGF-VX2 tumors (p<0.0105) and negatively correlated with the bFGF concentration of tumors (ρ=-0.903, p<0.0067).

Conclusion: The overexpression of bFGF in VX2 cells increased tumor viability and reduced necrosis, making the evaluation of long-term anticancer therapies possible in this model.

Keywords: VEGF; VX2; animal models; bFGF; clones; experimental tumors; necrosis; plasmid; rabbit; transfection; vessel density.