Insulin-like growth factor-binding protein 3 inhibits growth of experimental colocarcinoma.
BACKGROUND
We have previously shown that an important cell growth regulatory protein, insulin-like growth factor-binding protein 3 (IGFBP-3) is depleted in peripheral blood after open--but not laparoscopic--surgery. We have also demonstrated that IGFBP-3 induces apoptosis of human colon cancer cells in vitro. We report here the effect of IGFBP-3 on the growth of colonic epithelial cells in vivo.


METHODS
Two tumor models were used: chemically induced carcinogenesis with azoxymethane (AOM) and inoculation of syngeneic colon cancer cells. In AOM-induced carcinogenesis, wild type (WT) and IGFBP-3 transgenic (IGFBP-3-TG) CD1 mice were injected with AOM and the number of aberrant crypt foci (ACF) in the colon studied. In the syngeneic model, BALB/c mice were inoculated with CT26 cells. The control group received saline, while the test group was administered IGFBP-3 weekly. Tumor weight was assessed 2.5 weeks after establishment.


RESULTS
The number of aberrant crypt foci was significantly lower in IGFBP-3 transgenic mice (1.3 +/- 1.1) compared to WT controls (6.8 +/- 6.0) (P < .001). Further, CT26 tumors were significantly smaller in BALB/c mice that received IGFBP-3 (0.364 +/- 0.165 g) than in WT controls (0.742 +/- 0.261 g) (P < .01).


CONCLUSIONS
IGFBP-3 inhibits the development of colonic tumors in experimental models and may hold promise as an adjuvant therapy for patients with neoplasms.
Department of Surgery, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Irena
I
Kirman
Natalia
N
Poltoratskaia
Patricia
P
Sylla
Richard L
RL
Whelan
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000494:pharmacology
D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins