Skip to main content
Top
Published in: World Journal of Surgical Oncology 1/2007

Open Access 01-12-2007 | Research

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

Authors: Rajaraman Durai, Shi Y Yang, Alexander M Seifalian, Geoffrey Goldspink, Marc C Winslet

Published in: World Journal of Surgical Oncology | Issue 1/2007

Login to get access

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
Appendix
Available only for authorised users
Literature
1.
2.
go back to reference Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE: The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev. 2000, 21: 215-244. 10.1210/er.21.3.215.CrossRefPubMed Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE: The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev. 2000, 21: 215-244. 10.1210/er.21.3.215.CrossRefPubMed
3.
go back to reference Durai R, Davies M, Yang W, Yang SY, Seifalian A, Goldspink G, Winslet M: Biology of insulin-like growth factor binding protein-4 and its role in cancer (review). Int J Oncol. 2006, 28: 1317-1325.PubMed Durai R, Davies M, Yang W, Yang SY, Seifalian A, Goldspink G, Winslet M: Biology of insulin-like growth factor binding protein-4 and its role in cancer (review). Int J Oncol. 2006, 28: 1317-1325.PubMed
4.
go back to reference Rajaram S, Baylink DJ, Mohan S: Insulin-Like Growth Factor-Binding Proteins in Serum and Other Biological Fluids: Regulation and Functions. Endocr Rev. 1997, 18: 801-831. 10.1210/er.18.6.801.PubMed Rajaram S, Baylink DJ, Mohan S: Insulin-Like Growth Factor-Binding Proteins in Serum and Other Biological Fluids: Regulation and Functions. Endocr Rev. 1997, 18: 801-831. 10.1210/er.18.6.801.PubMed
5.
go back to reference Durai R, Yang SY, Sales KM, Seifalian AM, Goldspink G, Winslet MC: 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. 2007, 9: 625-631. 10.1111/j.1463-1318.2006.01190.x.CrossRefPubMed Durai R, Yang SY, Sales KM, Seifalian AM, Goldspink G, Winslet MC: 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. 2007, 9: 625-631. 10.1111/j.1463-1318.2006.01190.x.CrossRefPubMed
6.
go back to reference Sawaoka H, Kawano S, Tsuji S, Tsujii M, Gunawan ES, 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. 1998, 274: G1061-G1067.PubMed Sawaoka H, Kawano S, Tsuji S, Tsujii M, Gunawan ES, 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. 1998, 274: G1061-G1067.PubMed
7.
go back to reference Takei Y, Marzi I, Kauffman FC, Currin RT, Lemasters JJ, Thurman RG: Increase in survival time of liver transplants by protease inhibitors and a calcium channel blocker, nisoldipine. Transplantation. 1990, 50: 14-20. 10.1097/00007890-199007000-00003.CrossRefPubMed Takei Y, Marzi I, Kauffman FC, Currin RT, Lemasters JJ, Thurman RG: Increase in survival time of liver transplants by protease inhibitors and a calcium channel blocker, nisoldipine. Transplantation. 1990, 50: 14-20. 10.1097/00007890-199007000-00003.CrossRefPubMed
8.
go back to reference Mills SJ, Mathers JC, Chapman PD, Burn J, Gunn A: Colonic crypt cell proliferation state assessed by whole crypt microdissection in sporadic neoplasia and familial adenomatous polyposis. Gut. 2001, 48: 41-46. 10.1136/gut.48.1.41.PubMedCentralCrossRefPubMed Mills SJ, Mathers JC, Chapman PD, Burn J, Gunn A: Colonic crypt cell proliferation state assessed by whole crypt microdissection in sporadic neoplasia and familial adenomatous polyposis. Gut. 2001, 48: 41-46. 10.1136/gut.48.1.41.PubMedCentralCrossRefPubMed
9.
go back to reference Robbins S, Cotran R, Kumar V: cellular injury and cellular death. Pocket companian to Robbins Pathologic Basis Of Disease. 1995, W.B.Saunders Company, 8-9. 2 Robbins S, Cotran R, Kumar V: cellular injury and cellular death. Pocket companian to Robbins Pathologic Basis Of Disease. 1995, W.B.Saunders Company, 8-9. 2
10.
go back to reference Rojo MC, Gonzalez ME: In situ detection of apoptotic cells by TUNEL in the gill epithelium of the developing brown trout (Salmo trutta). J Anat. 1998, 193 ( Pt 3): 391-398. 10.1046/j.1469-7580.1998.19330391.x.CrossRef Rojo MC, Gonzalez ME: In situ detection of apoptotic cells by TUNEL in the gill epithelium of the developing brown trout (Salmo trutta). J Anat. 1998, 193 ( Pt 3): 391-398. 10.1046/j.1469-7580.1998.19330391.x.CrossRef
11.
go back to reference Nickerson T, Huynh H, Pollak M: Insulin-like growth factor binding protein-3 induces apoptosis in MCF7 breast cancer cells. Biochem Biophys Res Commun. 1997, 237: 690-693. 10.1006/bbrc.1997.7089.CrossRefPubMed Nickerson T, Huynh H, Pollak M: Insulin-like growth factor binding protein-3 induces apoptosis in MCF7 breast cancer cells. Biochem Biophys Res Commun. 1997, 237: 690-693. 10.1006/bbrc.1997.7089.CrossRefPubMed
12.
go back to reference Kooijman R: Regulation of apoptosis by insulin-like growth factor (IGF)-I. Cytokine Growth Factor Rev. 2006, 17: 305-323. 10.1016/j.cytogfr.2006.02.002.CrossRefPubMed Kooijman R: Regulation of apoptosis by insulin-like growth factor (IGF)-I. Cytokine Growth Factor Rev. 2006, 17: 305-323. 10.1016/j.cytogfr.2006.02.002.CrossRefPubMed
13.
go back to reference Zhang L, Yu J, Park BH, Kinzler KW, Vogelstein B: Role of BAX in the apoptotic response to anticancer agents. Science. 2000, 290: 989-992. 10.1126/science.290.5493.989.CrossRefPubMed Zhang L, Yu J, Park BH, Kinzler KW, Vogelstein B: Role of BAX in the apoptotic response to anticancer agents. Science. 2000, 290: 989-992. 10.1126/science.290.5493.989.CrossRefPubMed
14.
go back to reference Hong F, Kwon SJ, Jhun BS, Kim SS, Ha J, Kim SJ, Sohn NW, Kang C, Kang I: Insulin-like growth factor-1 protects H9c2 cardiac myoblasts from oxidative stress-induced apoptosis via phosphatidylinositol 3-kinase and extracellular signal-regulated kinase pathways. Life Sci. 2001, 68: 1095-105. 10.1016/S0024-3205(00)01012-2.CrossRefPubMed Hong F, Kwon SJ, Jhun BS, Kim SS, Ha J, Kim SJ, Sohn NW, Kang C, Kang I: Insulin-like growth factor-1 protects H9c2 cardiac myoblasts from oxidative stress-induced apoptosis via phosphatidylinositol 3-kinase and extracellular signal-regulated kinase pathways. Life Sci. 2001, 68: 1095-105. 10.1016/S0024-3205(00)01012-2.CrossRefPubMed
15.
go back to reference Ness JK, Scaduto RC, Wood TL: IGF-I prevents glutamate-mediated bax translocation and cytochrome C release in O4+ oligodendrocyte progenitors. Glia. 2004, 46: 183-94. 10.1002/glia.10360.CrossRefPubMed Ness JK, Scaduto RC, Wood TL: IGF-I prevents glutamate-mediated bax translocation and cytochrome C release in O4+ oligodendrocyte progenitors. Glia. 2004, 46: 183-94. 10.1002/glia.10360.CrossRefPubMed
16.
go back to reference Linseman DA, Phelps RA, Bouchard RJ, Le SS, Laessig TA, McClure ML, Heidenreich KA: Insulin-like growth factor-I blocks Bcl-2 interacting mediator of cell death (Bim) induction and intrinsic death signaling in cerebellar granule neurons. J Neurosci. 2002, 22: 9287-97.PubMed Linseman DA, Phelps RA, Bouchard RJ, Le SS, Laessig TA, McClure ML, Heidenreich KA: Insulin-like growth factor-I blocks Bcl-2 interacting mediator of cell death (Bim) induction and intrinsic death signaling in cerebellar granule neurons. J Neurosci. 2002, 22: 9287-97.PubMed
17.
go back to reference Lakhani SA, Masud A, Kuida K, Porter GA, Booth CJ, Mehal WZ, Inayat I, Flavell RA: Caspases 3 and 7: key mediators of mitochondrial events of apoptosis. Science. 2006, 311: 847-851. 10.1126/science.1115035.PubMedCentralCrossRefPubMed Lakhani SA, Masud A, Kuida K, Porter GA, Booth CJ, Mehal WZ, Inayat I, Flavell RA: Caspases 3 and 7: key mediators of mitochondrial events of apoptosis. Science. 2006, 311: 847-851. 10.1126/science.1115035.PubMedCentralCrossRefPubMed
18.
go back to reference Durai R, Yang SY, Sales KM, Seifalian AM, Goldspink G, Winslet MC: 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, 30: 883-888.PubMed Durai R, Yang SY, Sales KM, Seifalian AM, Goldspink G, Winslet MC: 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, 30: 883-888.PubMed
Metadata
Title
Role of insulin-like growth factor binding protein-4 in prevention of colon cancer
Authors
Rajaraman Durai
Shi Y Yang
Alexander M Seifalian
Geoffrey Goldspink
Marc C Winslet
Publication date
01-12-2007
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2007
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/1477-7819-5-128

Other articles of this Issue 1/2007

World Journal of Surgical Oncology 1/2007 Go to the issue