Antitumor effect of a specific aromatase inhibitor, 1-methyl-androsta-1,4-diene-3,17-dione (atamestane), in female rats bearing DMBA-induced mammary tumors.
Atamestane is a potent competitive inhibitor of estrogen biosynthesis (aromatase) in several species, in vitro and in vivo, and has no endocrine side effects. In this study, the efficacy of atamestane in suppressing tumor growth was evaluated in comparing with that of a non-steroidal aromatase inhibitor (CGS 16949A, Ciba-Geigy) and ovariectomy. Female Sprague-Dawley rats bearing DMBA-tumors were treated s.c. once daily either with 30 or 150 mg/kg atamestane or with 0.1 or 0.5 mg/kg CGS 16949A for 4 weeks. At these biologically equivalent doses both aromatase inhibitors effectively inhibited tumor growth: at the end of treatment they caused a marked reduction in tumor size (up to 70%), while ovariectomy led to a complete remission of tumor growth. The histo-morphological pictures of the mammary tumors from treated animals were qualitatively almost similar to those of the control. In hosts, neither compound exerted any influence on the weight of genital organs (ovary, uterus and vagina), although the peripheral LH levels were significantly elevated by the higher dose of the aromatase inhibitors. This effect on LH levels is probably due to the elimination of the negative feed-back effect of estrogens on gonadotropin secretion (counter regulation). The serum prolactin levels were decreased by the aromatase inhibitors, indicating a diminution of estrogen levels in the treated animals. The present results clearly demonstrate that, in spite of the counter regulation, a pure aromatase inhibitor such as atamestane in sufficiently high doses is able to inhibit the growth of DMBA-induced mammary tumors in intact female rats.
Nishino
Y
Y
Research Laboratory of Schering AG, West Berlin, F.R.G.
Schneider
M R
MR
Michna
H
H
el Etreby
M F
MF
D015127:9,10-Dimethyl-1,2-benzanthracene; D000735:Androstenedione / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D017316:Fadrozole; D005260:Female; D007093:Imidazoles / Q000627:therapeutic use*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D009570:Nitriles / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D007093:Imidazoles; D009570:Nitriles; D000735:Androstenedione; D015127:9,10-Dimethyl-1,2-benzanthracene; C048751:atamestane; D017316:Fadrozole