title: Potentiation of antiproliferative activity by mixtures of human recombinant IFN-alpha 2 and -gamma on growth of human cancer nodules maintained in continuous organotypic culture.
abstract: Alveolar II pulmonary tumor cells (A549 cells) maintained in continuous tridimensional organotypic culture were used to evaluate the eventual potentiation effect of mixtures of recombinant human interferon-alpha 2 and -gamma on growth inhibition of the tumor nodules. A continuous 45 day treatment (interferon renewed three times a week) with 10, 10(2) or 10(3) U/ml of IFN-alpha 2 or -gamma combined with a fixed high dose (10(3) U/ml) of either IFN-alpha 2 or -gamma resulted in an additive or synergistic growth inhibition according to the doses used. There was a close dose-effect relation, the percentage of inhibition increasing proportionally to the variable IFN doses added to the fixed high dose; moreover, the growth inhibition effect occurred earlier with the mixtures than with IFNs used separately. Furthermore, the growth inhibition observed with 2000 U/ml of the mixture (1000 U/ml of each IFN) was greater than that induced by 2000 U/ml of IFN-alpha 2 or -gamma used alone. A 35-day treatment with IFN-alpha 2 1000 U/ml plus IFN-gamma 1000 U/ml led to a complete growth inhibition and necrosis of the nodules. These data demonstrate that IFN-alpha 2 and -gamma cooperate to potentiate the IFN antiproliferative activity.
mesh_terms: D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000628:therapy*; D009924:Organ Culture Techniques; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma