Effect of the dual 5alpha-reductase inhibitor PNU 157706 on the growth of dunning R3327 prostatic carcinoma in the rat.
PNU 157706 [N-(1,1,1,3,3,3-hexafluorophenylpropyl)-3-oxo-4-aza-5alpha-androst-1-ene-17beta-carboxamide] is a novel, potent and selective dual 5alpha-reductase inhibitor. We have investigated its effect on tumor growth, endocrine organ weights and prostatic dihydrotestosterone (DHT) content in rats bearing the androgen dependent Dunning R3327 prostatic carcinoma. Animals with tumor diameters of about 1 cm were treated orally for 9 weeks with PNU 157706 (2 and 10 mg/kg/day, 6 days a week) or they were castrated, to check the hormone responsiveness of the tumor. PNU 157706 was effective at both doses tested in reducing tumor growth (53 and 51% inhibition at 2 and 10 mg/kg/day, respectively), while castration caused higher inhibition (82%) of tumor growth. A marked reduction of ventral prostate weight occurred in rats treated with both doses of PNU 157706 (75 and 78%) or castrated (91%). Seminal vesicle weight was also reduced by PNU 157706 administration (56 and 61% inhibition), whereas testes, adrenal, thymus and pituitary weights were not affected. Prostatic DHT content was markedly suppressed (85 and 91%) in PNU 157706 treated rats, compared to 95% suppression caused by castration. These data support a possible role of dual 5alpha-reductase inhibitors in the hormonal therapy of prostatic cancer.
Zaccheo
T
T
Experimental Endocrinology, Research/Oncology, Pharmacia and Upjohn, Nerviano (MI), Italy. tiziana.zaccheo@eu.pnu.com
Giudici
D
D
di Salle
E
E
D058891:5-alpha Reductase Inhibitors; D000736:Androstenes / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002369:Castration; D002455:Cell Division / Q000187:drug effects; D013196:Dihydrotestosterone / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004822:Epididymis / Q000187:drug effects; D008297:Male; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000628:therapy; D051381:Rats; D011919:Rats, Inbred Strains; D012669:Seminal Vesicles / Q000187:drug effects; D013737:Testis / Q000187:drug effects
D058891:5-alpha Reductase Inhibitors; D000736:Androstenes; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C112526:PNU 157706; D013196:Dihydrotestosterone