Inhibitory effect of the novel anti-estrogen EM-800 and medroxyprogesterone acetate on estrone-stimulated growth of dimethylbenz[a]anthracene-induced mammary carcinoma in rats
✍ Scribed by Shouqi Luo; Milos Stojanovic; Claude Labrie; Fernand Labrie
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- French
- Weight
- 153 KB
- Volume
- 73
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The novel anti-estrogen EM-800 and medroxyprogesterone acetate (MPA) inhibit estrone (E 1 )-stimulated growth of dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in a rat model. After 65 days, ovariectomy (OVX) decreased total tumor area to 9.6 ؎ 3.9% of initial size, while E 1 (1.0 µg, s.c., twice daily) stimulated tumor growth to 225 ؎ 40.9% of initial size. Daily oral administration of 2.5 mg/kg body weight of EM-800 completely abolished E 1 -stimulated tumor growth. A low daily dose of EM-800 (0.25 mg/kg body weight) or MPA (1 mg, s.c., twice daily) used alone partially reversed the stimulatory effect of E 1 on the growth of DMBA-induced tumors. The combination of both compounds, however, caused a more potent inhibitory effect than each compound used alone. A high dose of EM-800 completely or almost completely inhibited the E 1 -stimulated vaginal and uterine weights, respectively. The same dose of EM-800 completely reversed the inhibitory effect of E 1 on serum luteinizing hormone levels. Uterine, vaginal and tumoral estrogen and progesterone receptor levels were reduced markedly following treatment with EM-800. Our data show that the combination of the pure anti-estrogen EM-800 with the androgenic compound MPA achieves greater inhibition of the growth of DMBA-induced mammary carcinoma than that achieved by each compound used alone.