Breast Cancer Research and Treatment

, Volume 33, Issue 3, pp 237–244 | Cite as

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

  • Fernand Labrie
  • Shengmin Li
  • Claude Labrie
  • Charles Lévesque
  • Yves Mérand
Report

Summary

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′α-chloro-3′,17′α-dihydroxy-estra-1′,3′,5′-(10′)-trien-7′α-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 17β-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 µg (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 µg (twice daily), 20 days of treatment with EM-170 reversed by 55% the stimulatory effect of E1 (1.0 µg, subcutaneously, twice daily) on tumor growth in OVX animals. On the other hand, the antiestrogen also induced a significant inhibitory effect on 17β-hydroxysteroid dehydrogenase (17β-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. The present data show that the new steroidal antiestrogen EM-170 exerts a potent inhibitory effectin vivo on E1-stimulated growth of DMBA-induced mammary tumors, an effect that is probably mediated by both its antiestrogenic activity at the receptor level and its inhibitory effect on 17β-HSD, thus inhibiting local E2 formation and facilitating the action of the antiestrogen at the receptor level.

Key words

breast cancer steroidal antiestrogen pure antiestrogen DMBA tumors estradiol estrone 

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Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • Fernand Labrie
    • 1
  • Shengmin Li
    • 1
  • Claude Labrie
    • 1
  • Charles Lévesque
    • 1
  • Yves Mérand
    • 1
  1. 1.Medical Research Council Group in Molecular EndocrinologyCentre Hospitalier de l'Université Laval Research Center and Laval UniversityQuébecCanada

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