Long-term inhibitory effects of a novel anti-estrogen on the growth of ZR-75-1 and MCF-7 human breast cancer tumors in nude mice.
The effects of the novel anti-estrogen EM-343 on the growth of 2 hormone-responsive human breast cancer tumors have been examined in athymic nude mice. At the low daily dose of 5 microg, EM-343 administered subcutaneously for 6 months completely blocked the stimulatory effect of endogenous estrogens on the growth of ZR-75-1 and MCF-7 tumors implanted in nude mice. In addition, uterine weight decreased by 60% while ovarian weight increased by 37%. Estrogen receptor (ER) levels measured by [3H]-labeled estrogen binding were markedly reduced (by 96%, 96% and 92%) in ZR-75-1 and MCF-7 tumors, and in the mouse uterus, respectively. Accompanying the decrease in ER, progesterone receptor levels were reduced by 79%, 87% and 76%, respectively, in the above-mentioned tissues following EM-343 treatment. Our data show the pure anti-estrogenic properties of EM-343 and its high potency as an inhibitor of growth of human ZR-75-1 and MCF-7 breast tumors in nude mice.
Luo
S
S
Laboratory of Molecular Endocrinology, CHUL Research Center, Quebec, Canada.
Martel
C
C
Gauthier
S
S
Mérand
Y
Y
Bélanger
A
A
Labrie
C
C
Labrie
F
F
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003600:Cytosol / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D010880:Piperidines / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000473:pathology
D001578:Benzopyrans; C109371:EM 343; D004965:Estrogen Antagonists; D010880:Piperidines; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone