Increased radiosensitivity by a combination of 9-cis-retinoic acid and interferon-y in breast cancer cells.
Interferons (IFNs) and retinoic acid (RA) are known to possess antiproliferative effects in various human cancer cell lines, including squamous cervix carcinoma and breast cancer cell lines. Frequently synergistic effects could be observed by the combination of both, and in clinical trials high response rates could be achieved by IFN-alpha in combination with 13-cis-RA in patients with squamous carcinoma of the uterine cervix. Since radiation-potentiating effects of IFNs and RA were described, we evaluated the additional impact of irradiation on three human breast cancer cell lines and investigated the antiproliferative effects 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 either IFN-gamma or 9-cis-RA with irradiation resulted mostly in additive effects. Irradiation contributed additive or further synergistic effects to the already synergistic effects of the combination of these two drugs. Thus synergism of IFN-gamma and 9-cis-RA always at least persisted fully. These results suggest that a regimen of IFN, RA, and radiotherapy (RT) might be a promising combination in the therapy of solid tumors, where RT is part of the conventional treatment.
Windbichler
G H
GH
Department of Obstetrics and Gynecology, University Hospital, Innsbruck, Austria.
Hensler
E
E
Widschwendter
M
M
Posch
A
A
Daxenbichler
G
G
Fritsch
E
E
Marth
C
C
D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology* / Q000627:therapeutic use; D007641:Keratolytic Agents / Q000494:pharmacology; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007641:Keratolytic Agents; D011838:Radiation-Sensitizing Agents; D011994:Recombinant Proteins; D014212:Tretinoin; D007371:Interferon-gamma