Growth inhibition of DMBA-induced rat mammary carcinomas by the antiandrogen flutamide.
Antiandrogens have sporadically been reported to exert antitumor activities in both pre- and post-menopausal breast cancer. To explore the possibility of using the pure antiandrogen flutamide (FLU) in breast cancer therapy, rats bearing DMBA-induced mammary tumors were treated with FLU, dihydrotestosterone (DHT), or FLU plus DHT. FLU was administered orally, at doses comparable to those used in the treatment of prostate cancer patients. FLU-treated animals had a significantly smaller average tumor area than controls from day 11 up to the end of the experiment (day 20). A similar reduction of tumor growth was observed in rats given DHT and in those treated with DHT plus FLU. Plasma levels of LH, FSH, P, 17-OH P, E2 and DHEA measured at the end of experiment did not differ between treated animals and controls. Results demonstrate that the antiandrogen FLU and the full androgen DHT exert similar inhibitory effects on the growth of dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors. Moreover, data show that plasma steroids levels are unaffected by FLU treatment. This finding rules out any antitumor effect dependent on the reduction of adrenal and gonadal steroidosynthesis, and makes it appear more likely that androgen receptors are involved in the antiproliferative effect of FLU.
Boccuzzi
G
G
Università di Torino, Dipartimento di Fisiopatologia Clinica, Italy.
Tamagno
E
E
Brignardello
E
E
Di Monaco
M
M
Aragno
M
M
Danni
O
O
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D013196:Dihydrotestosterone / Q000627:therapeutic use; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005485:Flutamide / Q000008:administration & dosage / Q000627:therapeutic use*; D005640:Follicle Stimulating Hormone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D009929:Organ Size; D010053:Ovary / Q000187:drug effects; D011374:Progesterone / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects
D013196:Dihydrotestosterone; D011374:Progesterone; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D005485:Flutamide; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone