一种5α还原酶抑制剂或抗雄激素可防止大鼠微小前列腺癌发展为肉眼可见的癌。

A five-alpha reductase inhibitor or an antiandrogen prevents the progression of microscopic prostate carcinoma to macroscopic carcinoma in rats.

作者信息

Tsukamoto S, Akaza H, Onozawa M, Shirai T, Ideyama Y

机构信息

Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan.

出版信息

Cancer. 1998 Feb 1;82(3):531-7. doi: 10.1002/(sici)1097-0142(19980201)82:3<531::aid-cncr15>3.0.co;2-2.

DOI:10.1002/(sici)1097-0142(19980201)82:3<531::aid-cncr15>3.0.co;2-2

PMID:9452271

Abstract

BACKGROUND

The objective of this study was to elucidate the prophylactic effects of 5-alpha reductase inhibitor (e.g., finasteride) and a pure antiandrogen (e.g., casodex) on rat prostate carcinogenesis and to determine whether latent prostate carcinoma can be prevented to develop to clinically significant cancer by use of these drugs.

METHODS

F344 rats were subcutaneously administered 3,2'-dimethyl-4-aminobiphenyl (DMAB) for the first 20 weeks and testosterone propionate throughout the 60-week study. Finasteride (5 mg/kg and 15 mg/kg, 2 times per week) and casodex (15 mg/kg, 30 mg/kg, and 60 mg/kg, 3 times per week) were administered orally during the last 40 weeks of the study. Tumors were classified as visible prostate carcinoma when they could be recognized with the naked eye and as microscopic prostate carcinoma when detectable only with a microscope.

RESULTS

The incidence of visible prostate carcinoma was 51% (18 of 35 rats) in the positive control group, whereas it was 40% (4 of 10 rats) in the finasteride 5 mg/kg group, 16.7% (2 of 12 rats, P = 0.0091) in the finasteride 15 mg/kg group, 20% (4 of 20 rats, P = 0.05) in the casodex 15 mg/kg group, 14.3% (3 of 21 rats, P = 0.0008) in the casodex 30 mg/kg group, and 0% (0 of 11 rats, P = 0.0002) in the casodex 60 mg/kg group. On the other hand, when visible carcinomas and microscopic carcinomas were handled together, only casodex 60 mg/kg significantly inhibited the carcinogenesis rate.

CONCLUSIONS

Finasteride achieved dose-dependent inhibition of macroscopic rat prostate carcinogenesis, and casodex also inhibited macroscopic prostate carcinogenesis. However, both drugs showed insufficient prevention of carcinogenesis at the microscopic level. These findings indicate that, in clinical medicine as well, such drugs may also be able to prevent the progression of latent prostate carcinoma to life-threatening disease.

摘要

背景

本研究的目的是阐明5α还原酶抑制剂（如非那雄胺）和纯抗雄激素药物（如比卡鲁胺）对大鼠前列腺癌发生的预防作用，并确定使用这些药物是否可以预防潜伏性前列腺癌发展为具有临床意义的癌症。

方法

在为期60周的研究中，前20周对F344大鼠皮下注射3,2'-二甲基-4-氨基联苯（DMAB），并在整个研究期间注射丙酸睾酮。在研究的最后40周口服非那雄胺（5毫克/千克和15毫克/千克，每周2次）和比卡鲁胺（15毫克/千克、30毫克/千克和60毫克/千克，每周3次）。当肿瘤肉眼可见时分类为可见前列腺癌，仅在显微镜下可检测到时分类为微观前列腺癌。

结果

阳性对照组可见前列腺癌的发生率为51%（35只大鼠中的18只），而非那雄胺5毫克/千克组为40%（10只大鼠中的4只），非那雄胺15毫克/千克组为16.7%（12只大鼠中的2只，P = 0.0091），比卡鲁胺15毫克/千克组为20%（20只大鼠中的4只，P = 0.05），比卡鲁胺30毫克/千克组为14.3%（21只大鼠中的3只，P = 0.0008），比卡鲁胺60毫克/千克组为0%（11只大鼠中的0只，P = 0.0002）。另一方面，当将可见癌和微观癌一起处理时，只有比卡鲁胺60毫克/千克显著抑制了致癌率。