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

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Role of insulin-like growth factor binding protein-4 in prevention of colon cancer Rajaraman Durai1,2, Shi Y Yang1,2, Alexander M Seifalian*1,2, Geoffrey Goldspink1 and Marc C Winslet1,2 Address: 1Academic Division of Surgical and Interventional Sciences, University College London, London, UK and 2Royal Free Hampstead NHS Trust Hospital, London, UK Email: Rajaraman Durai - [email protected]; Shi Y Yang - [email protected]; Alexander M Seifalian* - [email protected]; Geoffrey Goldspink - [email protected]; Marc C Winslet - [email protected] * Corresponding author

Published: 7 November 2007 World Journal of Surgical Oncology 2007, 5:128

doi:10.1186/1477-7819-5-128

Received: 31 July 2007 Accepted: 7 November 2007

This article is available from: http://www.wjso.com/content/5/1/128 © 2007 Durai et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 IGFBP4, 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 Bcl2 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

Background Colon cancer is the second leading cause of morbidity and mortality in the developed countries [1]. Several treatment options are available for established colon cancer depending upon the stage of the disease. No proven treatment option is available to date in preventing the establishment and development of colon cancer other than prophylactic total colectomy. Colon cancer development

is influenced by several growth factors. Among these growth factors, insulin-like growth factor (IGF) system has been shown to play an important role in cancer d