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  • Title: Inhibitory effect of a steroidal antiestrogen (EM-170) on estrone-stimulated growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat.
    Author: Labrie F, Li S, Labrie C, Lévesque C, Mérand Y.
    Journal: Breast Cancer Res Treat; 1995 Mar; 33(3):237-44. PubMed ID: 7749151.
    Abstract:
    Recently, compounds having pure antiestrogenic activity have become available. In this study, we examined the activity of the new steroidal antiestrogen EM-170 (N-n-butyl, N-methyl-11-(16' alpha-chloro-3',17' alpha-dihydroxy-estra-1',3',5'-(10')-trien-7' alpha-yl) undecanamide) on the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma stimulated by treatment with estrone (E1), a steroid known to play an important role as precursor of 17 beta-estradiol (E2), especially in postmenopausal women. Twenty-five days after ovariectomy (OVX), tumor volume in control OVX animals decreased to 51.4 +/- 11% of the initial volume; treatment with E1, administered by Silastic implants, stimulated tumor growth to 179 +/- 21%. Treatment with the antiestrogen EM-170 at a dose of 200 micrograms (twice daily) not only completely reversed the stimulatory effect of E1, but also inhibited tumor growth to 30.5 +/- 9.6%, an effect that is 41% (P < 0.01 vs OVX control) greater than that of ovariectomy alone. At a relatively low dose of 40 micrograms (twice daily), 20 days of treatment with EM-170 reversed by 55% the stimulatory effect of E1 (1.0 micrograms, subcutaneously, twice daily) on tumor growth in OVX animals. On the other hand, the antiestrogen also induced a significant inhibitory effect on 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity in the DMBA-induced mammary tumors, an effect that is in agreement with the marked reduction caused by the same treatment on tumor estradiol (E2) levels in E1-treated OVX animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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