Effect of toremifene on the growth, hormone receptors and insulin-like growth factor-1 of hormone-dependent MCF-7 tumors in athymic mice.
Toremifene given in different sizes of silastic capsules was used to treat MCF-7 tumors in athymic mice. Toremifene inhibited the estradiol-stimulated growth of MCF-7 tumors in athymic mice. Average serum concentrations of toremifene obtained using a sustained-release preparation of the drug (in 0.5-, 1.0-, and 2.0-cm silastic capsules) increased gradually in a capsule-size-dependent fashion. Much higher levels of toremifene or N-demethyl-toremifene were detected in tumors (target tissues of estrogen) as compared with muscles (non-target tissues of estrogen). The concentration of toremifene in serum (i.e., 10-30 ng ml-1) was sufficient to inhibit the estrogen-stimulated growth of MCF-7 tumors at physiological (i.e., 200-400 pg ml-1) serum estradiol concentrations in premenopausal women. No significant difference in estrogen receptor (ER) levels was found between the estradiol-alone group and the toremifene-treated groups. However, the ER levels in the toremifene-alone group and the no-treatment group (no toremifene or estradiol) tended to increase as compared with the estradiol-alone group. Toremifene blocked the estradiol-induced increase in progesterone receptor levels in a dose-dependent fashion. Insulin-like growth factor-1 (IGF-1) levels in the MCF-7 tumors significantly decreased in the toremifene-alone group as compared with the estradiol-alone group. These results show the antiestrogenic action of toremifene on hormone-dependent MCF-7 tumors in athymic mice.
Iino
Y
Y
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
Takai
Y
Y
Ando
T
T
Sugamata
N
N
Maemura
M
M
Takeo
T
T
Ohwada
S
S
Morishita
Y
Y
D000818:Animals; D003692:Delayed-Action Preparations; D004343:Drug Implants; D004354:Drug Screening Assays, Antitumor; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D014018:Tissue Distribution; D017312:Toremifene / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D003692:Delayed-Action Preparations; D004343:Drug Implants; D004967:Estrogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D007334:Insulin-Like Growth Factor I; D017312:Toremifene