INCREASED RADIOSENSITIVITY BY A COMBINATION OF 9-CIS-RETINOIC ACID AND INTERFERON-GAMMA IN BREAST-CANCER CELLS

Interferons (IFNs) and retinoic acid (RA) are known to possess antipro liferative effects in various human cancer cell lines, including squam ous cervix carcinoma and breast cancer cell lines. Frequently synergis tic effects could be observed by the combination of both, and in clini cal trials high response rates could be achieved by IFN-alpha in combi nation with 13-cis-RA in patients with squamous carcinoma of the uteri ne cervix. Since radiation-potentiating effects of IFNs and RA were de scribed, we evaluated the additional impact of irradiation on three hu man breast cancer cell lines and investigated the antiproliferative ef fects of single, double, or triple treatments with IFN-gamma, 9-cis-RA , and irradiation. Antiproliferative effects were observed in all cell lines by any single treatment. When combining IFN-gamma with 9-cis-RA , synergism could be observed in all experiments. The combination of e ither IFN-gamma or 9-cis-RA with irradiation resulted mostly in additi ve effects. Irradiation contributed additive or further synergistic ef fects to the already synergistic effects of the combination of these t wo drugs. Thus synergism of IFN-gamma and 9-cis-RA always at least per sisted fully. These results suggest that a regimen of IFN, RA, and rad iotherapy (RT) might be a promising combination in the therapy of soli d tumors, where RT is part of the conventional treatment. (C) 1996 Aca demic Press, Inc.