Inhibition of angiogenic activity of renal carcinoma by an antisense oligonucleotide targeting fibroblast growth

Elisabetta Cenni1, Francesca Perut, Monia Zuntini

  • 1Laboratory for Pathophysiology of Orthopedic Implants, Istituti Ortopedici Rizzoli, Bologna, Italy. elisabetta.cenni@ior.it

Abstract

Insights

Antisense phosphorothioate oligodeoxynucleotide (PS-ODN2) targeting fibroblast growth factor-2 (FGF-2) minimally affected FGF-2 expression in renal carcinoma cells. However, PS-ODN2 significantly inhibited endothelial cell migration, suggesting a potential therapeutic avenue.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Fibroblast growth factor-2 (FGF-2) is a key inducer of angiogenesis.
  • Angiogenesis is essential for tumor growth and metastasis.

Purpose of the Study:

  • To evaluate the effect of blocking FGF-2 synthesis on the angiogenic activity of renal carcinoma cell lines.
  • To assess the efficacy of antisense phosphorothioate oligodeoxynucleotide (PS-ODN2) in inhibiting FGF-2 production and its downstream effects.

Main Methods:

  • Transfection of Caki-1 and CRBM-1990 cell lines with PS-ODN2.
  • Evaluation of FGF-2 mRNA and protein expression post-transfection.
  • Assessment of angiogenic activity, including endothelial cell migration, using conditioned media.

Main Results:

  • PS-ODN2 treatment resulted in non-significant decreases in FGF-2 expression in both cell lines.
  • Conditioned media from PS-ODN2-treated Caki-1 cells significantly reduced endothelial cell migration.
  • PS-ODN2 treatment decreased intracellular FGF-2 protein in CRBM-1990 cells but did not impair their ability to induce endothelial cell migration and proliferation.

Conclusions:

  • PS-ODN2 demonstrated minimal impact on FGF-2 expression in established renal carcinoma cell lines.
  • Despite minimal changes in FGF-2 levels, PS-ODN2 inhibited endothelial cell migration, indicating a potential anti-angiogenic effect.
  • The study suggests a complex interplay between FGF-2 expression and angiogenic potential in renal carcinoma.

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