COMBINED EFFECTS OF 13-CIS-RETINOIC ACID, TAMOXIFEN AND INTERFERON ONTHE GROWTH OF HUMAN BREAST-CANCER CELLS

We studied the effect of 13-cis-retinoic acid (13-cRA) alone and in co mbination with interferons (IFNs) and tamoxifen (TAM) in two establish ed human breast cancer cell lines: the estrogen-sensitive CG-5 and the estrogen-insensitive MDA-MB-453 cells. 13-cRA(10(-9)-10(-5) M) signif icantly reduced the growth of both cell lines in a dose-dependent fash ion, after 3 and 6 days of treatment. When the retinoid (10(-9)-10(-5) M) was combined with natural beta-IFN (100-1000 IU/ml) for 6 days, we observed a growth inhibition more pronounced than that produced by ea ch of the two single agents in both CG-5 and MDA-MB-453 cells, Only in the former model was the inhibitory effect synergistic at all the dru g concentrations used, Association of 13-cRA(10(-9)-10(-5) M) and reco mbinant alpha 2a-IFN (100-1000 IU/ml) or TAM (10(-7)-10(-6) M) did not determine an additive or synergistic effect on the growth of CG-5 cel ls.