EFFECT OF TOREMIFENE ON THE GROWTH, HORMONE RECEPTORS AND INSULIN-LIKE GROWTH FACTOR-I OF HORMONE-DEPENDENT MCF-7 TUMORS IN ATHYMIC MICE

Toremifene given in different sizes of silastic capsules was used to t reat MCF-7 tumors in athymic mice. Toremifene inhibited the estradiol- stimulated growth of MCF-7 tumors in athymic mice. Average serum conce ntrations of toremifene obtained using a sustained-release preparation of the drug (in 0.5-, 1.0-, and 2.0-cm silastic capsules) increased g radually in a capsule-size-dependent fashion. Much higher levels of to remifene or N-demethyl-toremifene were detected in tumors (target tiss ues of estrogen) as compared with muscles (non-target tissues of estro gen). The concentration of toremifene in serum (i. e., 10-30 ng ml-1) was sufficient to inhibit the estrogen-stimulated growth of MCF-7 tumo rs at physiological (i. e., 200-400 pg ml-1) serum estradiol concentra tions in premenopausal women. No significant difference in estrogen re ceptor (ER) levels was found between the estradiol-alone group and the toremifene-treated groups. However, the ER levels in the toremifene-a lone group and the no-treatment group (no toremifene or estradiol) ten ded to increase as compared with the estradiol-alone group. Toremifene blocked the estradiol-induced increase in progesterone receptor level s in a dose-dependent fashion. Insulin-like growth factor-1 (IGF-1) le vels in the MCF-7 tumors significantly decreased in the toremifene-alo ne group as compared with the estradiol-alone group. These results sho w the antiestrogenic action of toremifene on hormone-dependent MCF-7 t umors in athymic mice.