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

被引:16
作者
Durai R. [1 ,2 ]
Yang S.Y. [1 ,2 ]
Seifalian A.M. [1 ,2 ]
Goldspink G. [1 ]
Winslet M.C. [1 ,2 ]
机构
[1] Academic Division of Surgical and Interventional Sciences, University College London, London
[2] Royal Free Hampstead NHS Trust Hospital, London
关键词
Colon Cancer; Familial Adenomatous Polyposis; TUNEL Assay; Apoptotic Index; Secondary Antibody Conjugate;
D O I
10.1186/1477-7819-5-128
中图分类号
学科分类号
摘要
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. © 2007 Durai et al; licensee BioMed Central Ltd.
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共 18 条
[1]
Midgley R., Kerr D., Colorectal cancer, Lancet, 353, pp. 391-399, (1999)
[2]
Khandwala H.M., McCutcheon I.E., Flyvbjerg A., Friend K.E., The effects of insulin-like growth factors on tumorigenesis and neoplastic growth, Endocr Rev, 21, pp. 215-244, (2000)
[3]
Durai R., Davies M., Yang W., Yang S.Y., Seifalian A., Goldspink G., Winslet M., Biology of insulin-like growth factor binding protein-4 and its role in cancer (review), Int J Oncol, 28, pp. 1317-1325, (2006)
[4]
Rajaram S., Baylink D.J., Mohan S., Insulin-Like Growth Factor-Binding Proteins in Serum and Other Biological Fluids: Regulation and Functions, Endocr Rev, 18, pp. 801-831, (1997)
[5]
Durai R., Yang S.Y., Sales K.M., Seifalian A.M., Goldspink G., Winslet M.C., Increased apoptosis and decreased proliferation of colorectal cancer cells using insulin-like growth factor binding protein-4 gene delivered locally by gene transfer, Colorectal Dis, 9, pp. 625-631, (2007)
[6]
Sawaoka H., Kawano S., Tsuji S., Tsujii M., Gunawan E.S., Takei Y., Nagano K., Hori M., Cyclooxygenase-2 inhibitors suppress the growth of gastric cancer xenografts via induction of apoptosis in nude mice, Am J Physiol, 274, (1998)
[7]
Takei Y., Marzi I., Kauffman F.C., Currin R.T., Lemasters J.J., Thurman R.G., Increase in survival time of liver transplants by protease inhibitors and a calcium channel blocker, nisoldipine, Transplantation, 50, pp. 14-20, (1990)
[8]
Mills S.J., Mathers J.C., Chapman P.D., Burn J., Gunn A., Colonic crypt cell proliferation state assessed by whole crypt microdissection in sporadic neoplasia and familial adenomatous polyposis, Gut, 48, pp. 41-46, (2001)
[9]
Robbins S., Cotran R., Kumar V., Cellular injury and cellular death, Pocket Companian to Robbins Pathologic Basis Of Disease, pp. 8-9, (1995)
[10]
Rojo M.C., Gonzalez M.E., In situ detection of apoptotic cells by TUNEL in the gill epithelium of the developing brown trout (Salmo trutta), J Anat, 193, PART 3, pp. 391-398, (1998)