Role of insulin-like growth factor binding protein-4 in prevention of colon cancer

Rajaraman Durai¹^,2 , Shi Y Yang¹^,2 , Alexander M Seifalian¹^,2 , Geoffrey Goldspink¹ and Marc C Winslet¹^,2

¹Academic Division of Surgical and Interventional Sciences, University College London, London, UK

²Royal Free Hampstead NHS Trust Hospital, London, UK

author email corresponding author email

World Journal of Surgical Oncology 2007, 5:128doi:10.1186/1477-7819-5-128


Published:	7 November 2007

Abstract

Background

Insulin-like growth factors (IGFs) are important for the proliferation of cancer cells. One of their binding proteins, known as insulin-like growth factor binding protein -4 (IGFBP-4) is well known for its inhibitory action on IGFs in vitro. We assessed the effect of IGFBP-4 in prevention of development of colon cancer in vivo.

Methods

Nude mice were subcutaneously inoculated with HT-29 colon cancer cells and they were also simultaneously injected either gene construct containing mammalian expression vector pcDNA3 with or without IGFBP-4 gene or phosphate buffered saline. The effect was assessed 4 weeks later by evaluating the tumours for mitosis, necrosis, apoptosis, and expressions of IGFBP-4, Bcl-2 and Bax proteins.

Results

The results showed that the IGFBP-4 gene therapy did not prevent the tumour establishment but it increased the tumour apoptosis which was associated with an increase in Bcl-2 and Bax expressions. The IGFBP-4 protein was low in tumours which received IGFBP-4 gene construct which may be due to a feed back mechanism of IGFBP-4 upon its own cells.

Conclusion

IGFBP-4 gene therapy in the form localised gene transfer did not prevent colon cancer initiation and establishment but it resulted in increased apoptosis and Bax protein expression and a decrease in tumour cellular mitosis