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

  • Authors:
    • Rajaraman Durai
    • Shi Yu Yang
    • Kevin M. Sales
    • Alexander M. Seifalian
    • Geoffrey Goldspink
    • Marc C. Winslet
  • View Affiliations

  • Published online on: April 1, 2007     https://doi.org/10.3892/ijo.30.4.883
  • Pages: 883-888
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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.

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April 2007
Volume 30 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Durai, R., Yang, S.Y., Sales, K.M., Seifalian, A.M., Goldspink, G., & Winslet, M.C. (2007). Insulin-like growth factor binding protein-4 gene therapy increases apoptosis by altering Bcl-2 and Bax proteins and decreases angiogenesis in colorectal cancer. International Journal of Oncology, 30, 883-888. https://doi.org/10.3892/ijo.30.4.883
MLA
Durai, R., Yang, S. Y., Sales, K. M., Seifalian, A. M., Goldspink, G., Winslet, M. C."Insulin-like growth factor binding protein-4 gene therapy increases apoptosis by altering Bcl-2 and Bax proteins and decreases angiogenesis in colorectal cancer". International Journal of Oncology 30.4 (2007): 883-888.
Chicago
Durai, R., Yang, S. Y., Sales, K. M., Seifalian, A. M., Goldspink, G., Winslet, M. C."Insulin-like growth factor binding protein-4 gene therapy increases apoptosis by altering Bcl-2 and Bax proteins and decreases angiogenesis in colorectal cancer". International Journal of Oncology 30, no. 4 (2007): 883-888. https://doi.org/10.3892/ijo.30.4.883