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Published on: December 19, 2019
Promoting effects of antiandrogenic agents on rat ventral prostate carcinogenesis induced by
H Akaza1, S Tsukamoto, T Morita
1Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.
Abstract:
The objective of this study was to determine the effects of androgen depletion by 5alpha-reductase inhibitor (eg epristeride), pure antiandrogen (eg casodex) or C17-20 lyase inhibitor (eg YM116) on rat prostate carcinogenesis induced by administration of 3,2'-dimethyl-4-aminobiphenyl (DMAB). DMAB was subcutaneously administered on male F344 rats for the first 20 weeks. Epristeride (10 and 50 mg/kg, three times per week), casodex (15 and 30 mg/kg, three times per week) or YM116 (15 and 30 mg/kg, three times per week) were administered orally for 40 consecutive. Then, all accessory sex organs were studied for the formation of neoplastic lesions by histological examination. All carcinoma lesions were produced only in the ventral lobe of the prostate. The incidence of carcinoma developing in the ventral lobe of the prostate was 9.5% in the control group on which DMAB alone was administered, whereas it was 31.6% in the epristeride 10 mg/kg group. 45.0% in the epristeride 50 mg/kg group, 47.8% in the casodex 15 mg/kg group, 63.2% in the casodex 30 mg/kg group, 10.5% in the YM116 15 mg/kg group and 5.0% in the YM116 30 mg/kg group. The incidences of carcinoma in the epristeride 10 mg/kg group, casodex 15 mg/kg group and casodex 30 mg/kg group were significantly higher than that of the control group. In this experimental model, all ventral prostate carcinomas were in situ adenocarcinomas that did not form palpable nodules or distant metastasis. Epristeride and casodex showed a dose-dependent promoting effect on rat ventral prostate carcinogenesis. These results were contradictory to the results of our previous studies; exogenous testosterone in combination with DMAB produced palpable, and metastatic tumors in other portions of accessory sex organs of F344 rats but no carcinoma in ventral prostate, and those invasive carcinomas were significantly inhibited by 5alpha-reductase inhibitor and nonsteroidal anti-androgen. The action mechanisms of androgen and the effects of androgen-regulatory drugs on prostate carcinogenesis should be further studied. Prostate Cancer and Prostatic Diseases (2000) 3, 115-119
Insights
Androgen depletion drugs, epristeride and casodex, unexpectedly promoted rat ventral prostate cancer in a study. These findings contradict previous research and suggest further investigation into androgen
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- Prostate cancer development is influenced by androgens.
- The effects of androgen-depleting agents on prostate carcinogenesis are not fully understood.
- Previous studies suggested that androgen suppression inhibits prostate cancer.
Purpose of the Study:
- To investigate the impact of androgen depletion using 5alpha-reductase inhibitors, pure antiandrogens, and C17-20 lyase inhibitors on chemically induced rat prostate carcinogenesis.
- To compare the effects of epristeride, casodex, and YM116 on the incidence of ventral prostate carcinoma.
- To evaluate the dose-dependent effects of these agents on prostate tumor formation.
Main Methods:
- Male F344 rats were administered 3,2'-dimethyl-4-aminobiphenyl (DMAB) to induce prostate carcinogenesis.
- Rats received oral administration of epristeride, casodex, or YM116 at varying doses for 40 weeks.
- Accessory sex organs were histologically examined for neoplastic lesions, specifically ventral prostate carcinomas.
Main Results:
- The incidence of ventral prostate carcinoma was significantly higher in groups treated with epristeride (10 and 50 mg/kg) and casodex (15 and 30 mg/kg) compared to the control group.
- Epristeride and casodex demonstrated a dose-dependent promotion of rat ventral prostate carcinogenesis.
- YM116 showed a low incidence of carcinoma, with a slight decrease at the higher dose.
- All observed carcinomas were in situ adenocarcinomas without palpable nodules or distant metastasis.
Conclusions:
- Contrary to expectations, epristeride and casodex promoted ventral prostate carcinogenesis in this rat model.
- These findings challenge previous research indicating that androgen suppression inhibits prostate cancer.
- Further research is warranted to elucidate the complex mechanisms of androgen action and the role of androgen-regulatory drugs in prostate carcinogenesis.
