Effects of human recombinant interferons-alpha 2, -beta and -gamma on growth and survival of human cancer nodules maintained in continuous organotypic culture.
Alveolar II pulmonary tumor cells (A549 cells) maintained in continuous tridimensional organotypic culture were used to test the effects of recombinant human interferons -alpha 2, -beta and -gamma on growth inhibition and survival of the tumor nodules. The organotypic culture method has several advantages: the three-dimensional structures of the cells as well as some cell differentiation are maintained and the extremely low traumatizing culture conditions offer injured cells the maximum chance of survival. A continuous treatment lasting 65 days (three weekly interferon changes) with 10, 10(2), 10(3) and 10(4) U/ml doses of the three interferons led to growth inhibition and necrosis only in the presence of the two highest doses (10(3) and 10(4) U/ml) of IFN-alpha 2 and -gamma. IFN-beta had no inhibitory effect. Some nodules, especially at the lower dose levels (10(2) U/ml), showed enhanced growth in presence of the three types of interferons. After stopping the treatments, all the necrotic and disintegrating nodules resumed growth. Growth of the recovered nodules was followed in the absence of interferon for another period of 70 days. The growth rate of IFN-beta and -gamma-treated nodules was similar to that of the controls, but was slowed down for the regenerated IFN-alpha 2-treated nodules. Hence, in A549 organotypic cancer nodules and under our experimental conditions, only high doses of IFN-alpha 2 and -gamma appeared to have a partial cytolytic, but finally no tumoricidal action; IFN-beta was inactive. At the lower doses growth stimulation was found during the treatments with the three interferons.
Beaupain
R
R
Billard
C
C
Falcoff
E
E
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D013997:Time Factors
D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma; D007372:Interferons