COMBINED EFFECT OF TAMOXIFEN OR INTERFERON-BETA AND 4-HYDROXYPHENYLRETINAMIDE ON THE GROWTH OF BREAST-CANCER CELL-LINES

To improve the effectiveness of 4-hydroxyphenylretinamide (4-HPR), an analogue of retinoic acid used in chemoprevention and treatment of bre ast cancer, we investigated the effect of concomitant administration o f 4-HPR (0.1, 1 mu M) and tamoxifen (TAM, 0.1, 1 mu M), or 4-HPR and i nterferon-beta (IFN-beta, 10, 100, 500 IU/ml) on the growth of four ce ll lines (MCF7, T47D, MDA-MB231 and BT20) characterized by a different steroid receptor profile. A high concentration of 4-HPR caused a sign ificant inhibitory effect not only on the estrogen receptor-positive c ell lines (MCF7 and T47D), but also on one (BT20) of the two estrogen receptor-negative cell lines. IFN-beta displayed a dose-dependent inhi bitory effect in all cell lines, but it was most evident in MCF7 cells . In all cell lines, the combination of 4-HPR (0.1 mu M) and TAM (1 mu M) or IFN-beta (500 IU/ml) generally caused additive or synergistic e ffects. In particular, the finding that in estrogen receptor-negative MDA-MB231 cells 4-HPR (which at 1 mu M was singly ineffective) in comb ination with TAM at 1 mu M or any concentration of IFN-beta produced a synergistic effect suggests that the compound could act through a pat hway independent of specific receptors for retinoids. Our results indi cate that intrinsic characteristics of cells can influence responsiven ess to 4-HPR, TAM and IFN-beta singly or in association, ever within c ell lines with similar steroid receptor profiles. Thus. more attention should be paved to the biological characteristics of the single tumor in order to help choose the best combination of drugs to be applied.