THE EFFECT OF DROLOXIFENE ON THE INSULIN-LIKE GROWTH FACTOR-I-STIMULATED GROWTH OF BREAST-CANCER CELLS

Insulin-like growth factor-I (IGF-I) is an important mitogen in breast cancer. We studied here the effects of a new antiestrogen drug, drolo xifene (DROL, (E)-alpha-[p-[2-(dimethylamino) ethoxy]-phenyl]-alpha-et hyl-3-stilbenol) and tamoxifen (TAM) on the IGF-I-stimulated growth of estrogen receptor (ER) positive breast cancer cells, MCF-7 and their mechanism of action. IGF-I secretion from MCF-7 was increased by the a ddition of estrogen. Externally added IGF-I stimulated the growth of M CF-7 but not ER negative breast cancer cells, MDA-MB-231. DROL and TAM inhibited the IGF-I-stimulated growth of MCF-7. A 2 hr treatment with both drugs did not block IGF-I binding to the receptors in MCF-7. How ever, a 4 day treatment with DROL decreased the number of IGF-I recept ors without altering the binding affinity in MCF-7. These results sugg est that DROL can exert its antitumor activity against ER positive bre ast cancer not only by blocking the E(2) binding to the ER, but also b y counteracting the mitogenic effect of IGF-I.