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, droloxifene (DROL, (E)-alpha-[p-[2-(dimethylamino) ethoxy]-phenyl]-alpha'-ethyl-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 addition of estrogen. Externally added IGF-I stimulated the growth of MCF-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. However, a 4 day treatment with DROL decreased the number of IGF-I receptors without altering the binding affinity in MCF-7. These results suggest that DROL can exert its antitumor activity against ER positive breast cancer not only by blocking the E2 binding to the ER, but also by counteracting the mitogenic effect of IGF-I.
Pharmacological Res. Lab., Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
I
I
Kawamura
E
E
Lacey
T
T
Mizota
S
S
Tsujimoto
F
F
Nishigaki
T
T
Manda
K
K
Shimomura
D000970:Antineoplastic Agents / Q000633:toxicity*; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004965:Estrogen Antagonists / Q000633:toxicity*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011960:Receptors, Estrogen / Q000502:physiology; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000633:toxicity; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; C038345:droloxifene; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1