Synergistic antiproliferative effect of recombinant alpha-interferons with recombinant gamma-interferon.
Two human tumor cell lines were studied for their response to the antiproliferative effect of recombinant human interferons (IFNs) alpha 2, alpha 4, a hybrid alpha (delta 4 alpha 2 Bgl II alpha 1), and gamma, individually and in combination. Natural human alpha-IFN was used as a reference point for all experiments. RT4 (bladder carcinoma) cells were overall more sensitive to the antiproliferative effects of the IFNs than A2182 (lung adenocarcinoma) cells. Three-way analysis of variance indicated that the relative effectiveness of the alpha-IFNs was alpha 2 less than alpha 4 less than hybrid alpha less than natural alpha-IFN. On an international reference unit per milliliter basis, gamma-IFN was 50- and 75-fold more effective than natural alpha-IFN and hybrid alpha-IFN in RT4 cells and 5.6-, 12.1-, and 14.9-fold more effective than alpha 4-, hybrid alpha-, and natural alpha-IFN in A2182 cells. In contrast, when recalculated on a nanogram per milliliter basis, gamma-IFN was only threefold more effective than the hybrid alpha-IFN in RT4 and approximately twofold less effective than alpha 4 and the hybrid alpha in A2182. Combinations of alpha-IFNs gave additive or antagonistic effects. When any of the alpha-IFNs were combined with the gamma-IFN, however, a synergistic antiproliferative effect was seen. The magnitude of the synergy was dependent upon the concentration of gamma-IFN used and the type of alpha-IFN in the combination. Antagonistic effects were seen at the lowest gamma-IFN concentration studied (0.2 IRU/ml). Synergy also varied according to the potency of the alpha-IFN used.
D002277:Carcinoma / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage; D001749:Urinary Bladder Neoplasms / Q000473:pathology
D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma