Insulin-like growth factor binding protein-4 gene therapy increases apoptosis by altering Bcl-2 and Bax proteins and decreases angiogenesis in colorectal cancer

Int J Oncol. 2007 Apr;30(4):883-8.

Abstract

Insulin-like growth factors are known to inhibit apoptosis and promote tumour angiogenesis. Previously we have shown that insulin-like growth factor binding protein-4 (IGFBP-4) gene therapy increased apoptosis and decreased mitosis in colon cancer. In this experiment we used HT-29 colon cancer cells to induce subcutaneous cancers in nude mice and administered either the mammalian expression vector with IGFBP-4 insert or vector only around the tumour site. Three weeks after gene transfer, tumours were harvested and expressions of Bax, Bcl-2 and IGF-I receptor in tumours were determined by Western blotting and immunofluorescence. Micro-vessel counting was performed by immunostaining with CD34 and von Willebrand antibodies. Results showed that tumours treated with IGFBP-4 gene had higher expression of Bax, lower expression of Bcl-2 and IGF-I receptor. Bcl-2 was localised to tumour cell cytoplasm while Bax was expressed both in the interstitial area and cytoplasm. IGFBP-4 treatment also decreased micro-vessel count in tumour tissues. Micro-vessels were mainly located in the periphery and interstitial area. This experiment shows that IGFBP-4 gene therapy increases tumour apoptosis via altering the expressions of Bcl-2 and Bax and decreasing the angiogenesis in colorectal cancer.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Colorectal Neoplasms / blood supply*
  • Colorectal Neoplasms / therapy*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 4 / genetics*
  • Mice
  • Neovascularization, Pathologic / therapy*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / metabolism*

Substances

  • Insulin-Like Growth Factor Binding Protein 4
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein