© 1998 by Oxford University Press
Journal Of The National Cancer Institute, Vol 90, 772-778, Copyright © 1998 by Oxford University Press
S Couillard, C Labrie, A Belanger, B Candas, F Pouliot and F Labrie
BACKGROUND: In the mammary gland, androgens are formed from the precursor
steroid dehydroepiandrosterone (DHEA). Clinical evidence indicates that
androgens have inhibitory effects on breast cancer. Estrogens, on the other
hand, stimulate the development and growth of breast cancer. We studied the
effect of DHEA alone or in combination with the newly described pure
antiestrogen EM-800 on the growth of subcutaneous tumor xenografts formed
by the human breast cancer cell line ZR-75-1 in ovariectomized nude mice.
METHODS: Immediately after ovariectomy, mice received daily subcutaneous
injections of 0.5 microg estrone (E1) (an estrogenic hormone). EM-800 (15,
50, or 100 microg) was given orally once daily. DHEA was administered
percutaneously twice daily (total dose of 0.3, 1.0, or 3.0 mg) to the
dorsal skin either alone or in combination with a 15-microg daily oral dose
of EM-800. Changes in tumor size in response to the treatments (in relation
to measurements made on the first day of treatment) were assessed
periodically. At the end of the experiments, tumors were dissected and
weighed. RESULTS: A 9.4-fold increase in tumor size in 9.5 months was
observed in ovariectomized mice receiving E1 alone. Administration of 15,
50, or 100 microg EM-800 in E1-supplemented mice led to inhibitions of
87.5%, 93.5%, and 94.0% in tumor size, respectively. DHEA, on the other
hand, at doses of 0.3, 1.0, or 3.0 mg inhibited terminal tumor size by
50.4%, 76.8%, and 80.0%, respectively. Comparable inhibitions in tumor size
were obtained with a daily 15-microg oral dose of EM-800 with or without
different doses of percutaneous DHEA. CONCLUSIONS: DHEA and EM-800
independently suppressed the growth of E1-stimulated ZR-75-1 xenograft
tumors in nude mice. Administration of DHEA at the defined doses did not
alter the inhibitory effect of EM-800.
ARTICLES
Effect of dehydroepiandrosterone and the antiestrogen EM-800 on growth of human ZR-75-1 breast cancer xenografts
Laboratory of Molecular Endocrinology, CHUL Research Center and Laval University, Quebec, Canada.
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