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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
Author(s) -
Luo Shouqi,
Stojanovic Milos,
Labrie Claude,
Labrie Fernand
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19971114)73:4<580::aid-ijc20>3.0.co;2-c
Subject(s) - dmba , 7,12 dimethylbenz[a]anthracene , endocrinology , medicine , medroxyprogesterone acetate , estrogen , estrone , medroxyprogesterone , mammary tumor , luteinizing hormone , chemistry , hormone , cancer , breast cancer , carcinogenesis
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. Int. J. Cancer 73:580–586, 1997. © 1997 Wiley‐Liss, Inc.