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 tumor. PI not only inhibited in vitro growth of tumor cells but also suppressed 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 inhibitory 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-dependent manner. Daily injection of purified PI into tumor-bearing rats suppressed the tumor growth. A 58% reduction in tumor weight and a 2-fold reduction in tumor growth rate were observed over a 15-day treatment period. Continued treatment with PI significantly suppressed the tumor growth rate by nearly 3-fold. These findings clearly demonstrate a potential application of PI for treating human prostatic adenocarcinoma.
Lokeshwar
B L
BL
Department of Urology, School of Medicine, University of Miami, Florida.
Hurkadli
K S
KS
Sheth
A R
AR
Block
N L
NL
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007265:Inhibins / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D011467:Prostate; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D012661:Semen / Q000737:chemistry
D006131:Growth Inhibitors; D010446:Peptide Fragments; D007265:Inhibins