Differential effects of growth factor antagonists on neoplastic and normal prostatic cells

Abstract

Growth factors such as epidermal growth factor and fibroblast growth factor have been suggested to be involved as paracrine or autocrine mediators of androgen action in normal and malignant prostatic cells. Suramin and protamine are potent in vitro growth factor antagonists. To evaluate the effect of growth factor antagonists on prostatic growth, suramin and protamine were administered to castrated rats simultaneously receiving exogenous testosterone replacement in an attempt to block androgen-dependent restoration of the normal rat ventral prostate. Using this prostatic restoration model, there was no statistical difference in the prostate wet weight or total DNA content attained between rats given testosterone alone and those given testosterone in combination with either suramin or protamine. In intact rats, suramin administration caused an 80% reduction in serum testosterone; concomitantly, these rats had a 40% reduction in mean prostate weight. This decrease in size could be blocked with androgen supplementation. To examine the effects of growth factor antagonists on neoplastic prostatic cell growth, rats bearing the androgen-independent AT-2 subline of the Dunning R-3327 tumor were treated with either suramin or protamine. The same dosing regimen found to be ineffective in blocking the restoration of the involuted prostate of castrated rats resulted in a significant reduction in the growth rate of AT-2 tumors. These results suggest that the growth factor antagonists suramin and protamine given in vivo have a differential ability to slow the growth of malignant vs. normal prostatic cells.