Inhibition of angiogenic activity of renal carcinoma by an antisense oligonucleotide targeting fibroblast growth factor-2.

Background: Fibroblast growth factor-2 (FGF-2) induces angiogenesis, critical for the growth and metastatic spread of tumors.

Materials And Methods: The effect of blocking FGF-2 synthesis by an antisense phosphorothioate oligodeoxynucleotide (PS-ODN2) was evaluated on the angiogenic activity of Caki-1 and of a cell line isolated from a renal carcinoma bone metastasis (CRBM-1990). After the transfection with PS-ODN2, FGF-2 mRNA, protein expression and angiogenic activity were evaluated.

Results: In Caki-1, a not significant decrease in the released FGF-2 was observed after 72 hours. In CRBM-1990, a not significant decrease in intracellular FGF-2 protein was observed after 72 hours. Endothelial cell migration induced by the conditioned media from Caki-1 treated with PS-ODN2 for 72 hours was significantly reduced.

Conclusion: PS-ODN2 treatment of the established line Caki-1 induced minimal variations in FGF-2 expression, but inhibited endothelial cell migration. In CRBM-1990 cells, PS-ODN2 determined a decrease in intracellular protein without reducing the ability to induce endothelial cell migration and proliferation.