Interrelationships between dietary restriction, the IGF-I axis, and expression of vascular endothelial growth factor by prostate adenocarcinoma in rats.
Human studies suggest that excessive energy intake and obesity may influence prostate cancer progression. Rodent experiments demonstrate that diet restriction attenuates tumor growth in parallel with reduced vascular density. The present study examines changes in the insulin-like growth factor I (IGF-I) axis caused by dietary restriction and their association with the expression of vascular endothelial growth factor (VEGF) in prostate cancer. Weanling male Copenhagen rats were randomized into control or 40% dietary restricted groups (n = 5). After 8 wk, rats were implanted with rat AT6.3 prostate adenocarcinoma cells. Two weeks later, the animals were sacrificed and serum, normal prostate, liver, and prostate tumor samples were collected for analyses. Dietary restriction reduced serum concentrations of IGF-I by 35% (P < 0.05) and increased IGF-binding protein-3 (IGFBP3) by sevenfold (P < 0.0001). Lower circulating IGF-I concentrations were correlated with reduced IGF-I mRNA expression in the liver, the primary source of circulating IGF-I. Dietary restriction also lowered mRNA expression of IGF-I (45%, P = 0.0242) and its receptor IGFIR (40%, P = 0.0083) in prostate tumors. Similarly, reduced VEGF mRNA (30%, P = 0.0176) and secreted VEGF protein (33%, P = 0.0003) were observed in prostate cancer of restricted rats. An in vitro study employing AT6.3 prostate cancer cells demonstrated dose- and time-dependent stimulation of VEGF expression by IGF-I. These results suggest that dietary restriction reduces endocrine and prostate tumor autocrine/paracrine IGF-I expression, which contributes to reduced VEGF expression and signaling, to inhibit tumor angiogenesis associated with prostate tumorigenesis.
The Ohio State University Interdisciplinary Ph.D. Program in Human Nutrition (OSUN), The Ohio State University, Columbus, Ohio 43210, USA.
Anna A
AA
Powolny
Shihua
S
Wang
Peter S
PS
Carlton
Dahlys R
DR
Hoot
Steven K
SK
Clinton
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001835:Body Weight; D031204:Caloric Restriction; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D018972:Insulin-Like Growth Factor Binding Protein 3; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I