HUMAN PROSTATIC INHIBIN SUPPRESSES TUMOR-GROWTH AND INHIBITS CLONOGENIC CELL-SURVIVAL OF A MODEL PROSTATIC ADENOCARCINOMA, THE DUNNING R3327G RAT-TUMOR

Prostatic inhibin (PI) is a M(r) 10,700 protein found in human seminal plasma and is secreted by the prostate. Recognition of alteration of PI levels in prostatic diseases prompted us to investigate its effect on an animal prostatic adenocarcinoma model, the Dunning R3327G rat tu mor. PI not only inhibited in vitro growth of tumor cells but also sup pressed tumor growth in vivo. A dose- dependent inhibition of both the clonogenic cell growth and rate of proliferation (DNA synthesis) was observed in tumor cell cultures incubated with purified PI. These inhi bitory activities were similar in both androgen-dependent and androgen -independent, Dunning tumor cell lines. A functional decapeptide of PI was also found to inhibit Dunning tumor cell colonies in a dose-depen dent manner. Daily injection of purified PI into tumor-bearing rats su ppressed the tumor growth. A 58% reduction in tumor weight and a 2-fol d reduction in tumor growth rate were observed over a 15-day treatment period. Continued treatment with PI significantly suppressed the tumo r growth rate by nearly 3-fold. These findings clearly demonstrate a p otential application of PI for treating human prostatic adenocarcinoma .