Premium
Prevention of prostate‐related cancers in Lobund‐Wistar rats
Author(s) -
Pollard Morris
Publication year - 1999
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19990601)39:4<305::aid-pros12>3.0.co;2-y
Subject(s) - endocrinology , medicine , dihydrotestosterone , androgen , testosterone (patch) , prostate , prostate cancer , tamoxifen , hormone , isoflavones , cancer , breast cancer
BACKGROUND Since prostate cancer (PC) development involves a combination of genetic predisposition and promotional mechanisms, especially the metabolic conversion of testosterone to 5α dihydrotestosterone (DHT) by 5α reductase, how do mechanisms in man relate to prostate‐seminal vesicle (P‐SV) tumor development in Lobund‐Wistar (L‐W) rats? The disease in man and in L‐W rats shares developmental mechanisms and characteristics to the extent that prevention of P‐SV tumors in L‐W rats could be predictive of similar results in man. The epidemiology of PC in man and P‐SV tumors in L‐W rats indicates that both are hormone‐related diseases based on genetic predisposition, high production of androgens (which are activated to DHT by 5α reductase), and early development of androgen‐dependent and metastasizing late androgen‐independent stages of adenocarcinomas, all after long latency periods. METHODS L‐W rats at risk of developing spontaneous or induced P‐SV tumors were subjected to putative antitumor agents or procedures. These included dietary restriction, testosterone ablation, soybean‐derived isoflavones, antiangiogenic linomide, tamoxifen, and a vitamin D analogue. RESULTS L‐W rats subjected to 1) early onset of dietary restriction manifested suppression of spontaneous and induced development of P‐SV tumors; 2) testosterone‐ablation by nonesterified DHT (NE‐DHT) suppressed early onset of induced P‐SV tumors and to a lesser extent late onset of spontaneous tumors; 3) diets containing soy protein isolate (high isoflavones) manifested marginal suppressive effects against induced P‐SV tumors, but in 12‐month‐old rats, the development of spontaneous tumors was reduced in incidence; 4) early administrations of antiangiogenic linomide suppressed development of induced P‐SV tumors and of transplanted prostate adenocarcinoma III (PA‐III) tumors, but linomide had little antitumor effect against large advanced stage tumors; and 5) tamoxifen and vitamin D analogue suppressed development of P‐SV tumors. Results in conditions 1–3 were negative when tested against PA‐III tumors. CONCLUSIONS Developing stages of P‐SV tumors were prevented in L‐W rats with autochthonous spontaneous and induced tumors, but most of the agents tested were of no therapeutic benefit against advanced‐stage and transplanted PA‐III tumors. However, early administrations of antiangiogenic linomide suppressed early growth of induced and transplanted PA‐III tumors. Prostate 39:305–309, 1999. © 1999 Wiley‐Liss, Inc.