VEGF Trapon inhibits tumor growth in papillary thyroid carcinoma

Eur Rev Med Pharmacol Sci. 2015;19(2):235-40.

Abstract

Objective: Vascular endothelial growth factor (VEGF) is the most potent inducer of neovasculature, and its increased expression has been related to a worse clinical outcome in many disease. Angiogenesis from thyroid cancer cell plays the important roles in post-surgical persistent, recurrent, and metastatic papillary thyroid cancer (PTC). Vascular endothelial growth factor (VEGF) Trapon is a newly developed VEGF-blocking agent with stronger affinity and broader activity than the anti-VEGF antibody bevacizumab. In this study, we tested the activity of VEGF Trapon on a PTC model in vivo.

Materials and methods: BC-PAP (derived from papillary carcinomas) transfected with a luciferase-expressing vector were injected into the back to mice. I.p. treatment with VEGF Trapon or control protein (25 mg/kg twice weekly) was started shortly after tumor injection to prevent tumor development (prevention model) or after established tumors were formed to inhibit tumor growth and metastasis formation (intervention model).

Results: In the prevention model, VEGF Trapon inhibited tumor growth by 73 ± 12% compared with control (p = 0.014) and significantly prolonged survival. In the intervention model, VEGF Trapon inhibited tumor growth by 68 ± 7% (p < 0.01). Microvascular density was reduced by 56% due to VEGF Trapon treatment (p < 0.01).

Conclusions: VEGF Trapon is a potent inhibitor of BC-PAP tumor growth, angiogenesis and blocks the biological function of VEGF in vivo. These results support further clinical development of VEGF Trapon for PTC and other cancer types.

MeSH terms

  • Angiogenesis Inhibitors
  • Animals
  • Carcinoma / blood supply
  • Carcinoma / drug therapy*
  • Carcinoma, Papillary / blood supply
  • Carcinoma, Papillary / drug therapy*
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Pathologic / drug therapy
  • Recombinant Fusion Proteins / pharmacology*
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / blood supply
  • Thyroid Neoplasms / drug therapy*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Recombinant Fusion Proteins
  • VEGF Trapon
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A