Increased apoptosis and decreased proliferation of colorectal cancer cells using insulin-like growth factor binding protein-4 gene delivered locally by gene transfer.

Abstract

OBJECTIVE:

Insulin-like growth factor (IGF)-I induces proliferation of transformed cells. Its binding proteins (IGFBP) are involved in local regulation of IGF. This study assessed the effects of overexpression of IGFBP-4 on the development of cancer in vivo.

METHOD:

Nude mice were subcutaneously inoculated with HT-29 colorectal cancer cells (3 x 10(6)). When the tumour became visible (1 week after inoculation), animals received either 150 microg of mammalian expression vector containing IGFBP-4 cDNA or vector alone (n = 6 each) by peritumoural injection. Tumour size was measured during the growth. After 3 weeks of IGFBP-4 induction, animals were killed and tumour tissue samples were collected for examining the level of IGFBP-4 expression. Tumour mitotic activities were determined by counting numbers of mitotic cells on the tissue section. Apoptosis was investigated by terminal deoxynucleotidyl transferase-mediated dUDP nick end labelling assay.

RESULTS:

Following IGFBP-4 treatment, tumour showed large necrotic areas, significantly increased numbers of apoptotic cells (36.67 +/- 7.36 vs 7.07 +/- 1.91, P < 0.01 vs control), decreased cells undergoing mitosis (2.31 +/- 0.32 vs 3.61 +/- 0.27, P < 0.01 vs control) and higher expression of IGFBP-4 (P < 0.05 vs control).

CONCLUSION:

IGFBP-4 gene transfer increased apoptosis and decreased mitosis, but tumour volume was not significantly altered possibly due to cellular debris filling the centre of tumours.

• Authors: R Durai, S Y Yang, K M Sales, A M Seifalian, G Goldspink, M C Winslet
• Journal: Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland (Colorectal Dis) Vol. 9 Issue 7 Pg. 625-31 (Sep 2007) ISSN: 1462-8910 [Print] England
• PMID: 17824980 (Publication Type: Journal Article)

Chemical References

• DNA, Complementary
• Insulin-Like Growth Factor Binding Protein 4

Topics

• Animals
• Apoptosis
• Cell Line, Tumor
• Cell Proliferation
• Colorectal Neoplasms (pathology, therapy)
• DNA, Complementary (metabolism)
• Gene Expression Regulation, Neoplastic
• Gene Transfer Techniques
• Genetic Therapy (methods)
• Humans
• Insulin-Like Growth Factor Binding Protein 4 (genetics, therapeutic use)
• Mice
• Mice, Nude
• Mitosis
• Protein Binding