Inhibition of hormone-dependent and independent breast cancer cell growth in vivo and in vitro with the antiestrogen toremifene and recombinant human interferon-alpha 2.
The antiproliferative action of the antiestrogen toremifene and recombinant human interferon-alpha 2a (IFN-alpha 2a) were examined on human breast cancer cell lines grown in culture and in the athymic mouse. Solid tumors grew from an inoculation of a 99:1 ratio of hormone dependent (MCF-7) and hormone independent (MDA-MB-231) breast cancer cells without estrogen administration. However, estradiol supplementation significantly increased the rate of tumor growth. The daily administration of 1.35 x 10(6) U of recombinant human IFN-alpha 2a resulted in a marked rduction of tumor growth in both estradiol-treated and non-treated mice. Toremifene administration (130 micrograms/day from a sustained release preparation) markedly inhibited estradiol stimulation of mouse uterine weight and partially reduced estradiol-stimulated tumor growth. The combination of IFN-alpha 2a (1.35 x 10(6) u/day) with toremifene (130 micrograms/day) reduced estradiol-stimulated growth much below that of toremifene alone but not below that seen with interferon alone. Toremifene (10(-10)-10(-6) M) did not inhibit the growth of hormone-independent MDA-MB-231 breast cancer cells in vitro whereas it did inhibit the growth of hormone-dependent MCF-7 cells in phenol red containing media. IFN-alpha 2a (1-10,000 u) inhibited the growth of both MCF-7 and MDA-MB-231 cells in culture; however, MCF-7 cells were approximately 10-fold more sensitive to interferon inhibition. This was consistent with the MCF-7 cells showing a greater sensitivity to interferon than MDA-MB-231 cells in the induction of 2'5'-oligoadenylate synthetase.(ABSTRACT TRUNCATED AT 250 WORDS)
Robinson
S P
SP
Department of Human Oncology, University of Wisconsin, Madison 53792.
Goldstein
D
D
Witt
P L
PL
Borden
E C
EC
Jordan
V C
VC
D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004354:Drug Screening Assays, Antitumor; D004965:Estrogen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D004967:Estrogens / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D011994:Recombinant Proteins; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017312:Toremifene; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004965:Estrogen Antagonists; D004967:Estrogens; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D013629:Tamoxifen; D017312:Toremifene