Enhanced efficacy in anti-tumour activity by combined therapy of recombinant FGFR-1 related angiogenesis and low-dose cytotoxic agent

Eur J Cancer. 2007 Sep;43(14):2134-9. doi: 10.1016/j.ejca.2007.07.014. Epub 2007 Aug 27.

Abstract

Fibroblast growth factor receptor-1 (FGFR-1) has been used as a target for anti-angiogeneic therapy of cancer. The strategies of combining anti-angiogenic biotherapy with chemotherapeutic drugs show potential and promise for cancer therapy. In this study, we evaluated the anti-tumour efficacy of chicken FGFR-1 (cFR-1) vaccine combined with low-dose gemcitabine in two mice tumour models. We found that both the cFR-1 vaccine and low-dose gemcitabine can suppress tumour growth to some extent. Remarkably, the combination strategy produces an apparent decrease in tumour volume, microvessel density and tumour cell proliferation, and an increase of apoptosis without obvious side-effects compared with either therapy alone. Moreover, the combination strategy also demonstrated synergistic indices against tumour growth and angiogenesis. Furthermore, auto-antibodies against mouse FGFR-1 were identified. These findings support the idea that the combination strategy synergistically strengthens anti-tumour activity via suppression of tumour angiogenesis without overt toxicity in tumour-bearing mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Autoimmunity
  • Cancer Vaccines / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Drug Synergism
  • Female
  • Gemcitabine
  • Immunohistochemistry
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Neoplasms / drug therapy*
  • Neovascularization, Pathologic / drug therapy*
  • Receptor, Fibroblast Growth Factor, Type 1 / administration & dosage
  • Recombinant Proteins / administration & dosage

Substances

  • Angiogenesis Inhibitors
  • Cancer Vaccines
  • Recombinant Proteins
  • Deoxycytidine
  • Receptor, Fibroblast Growth Factor, Type 1
  • Gemcitabine