Treatment with human recombinant leukocyte interferons inhibitsin vitro invasive ability of human lung carcinoma cells

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Abstract
The effects of treatment of human lung carcinoma cell line A 549 with recombinant DNA-derived human leukocyte interferons A (rIFN-αA) or D (rIFN-αD), and human lymphoblastoid interferon (Wellferon) onin vitro cell invasion were investigated in a quantitative invasion assay using human amnion. The A 549 cells treated with IFN for one day were incubated on the denuded basement membrane of the amnion in the absence of IFN, and cells which penetrated the full thickness of the connective tissue barrier were measured after 4 days. A dose-dependent inhibition of cell invasion was produced by the recombinant IFNs.The one day treatment of cells with 2·4 × 103 to 1·8 × 104 units/ml of rIFN-αA resulted in a 60–80 per cent inhibition of invasiveness compared to untreated cells. After a one day exposure of cells to 2·2 × 104 units/ml of rIFN-αD, cell invasion was reduced by approximately 70 per cent; a concentration of 4·4 × 103 units/ml had no apparent effect. Similar treatment with lymphoblastoid IFN (6 × 104 units/ml) had no significant effect on cell invasion. Accompanying the one day exposure to rIFN-αA (1·8 × 104 units/ml) or rIFN-αD (2·2 × 104 units/ml), (2′, 5′) oligo (A) synthetase activity was induced approximately 20-fold; a 4-fold induction of enzyme activity was found in cells exposed to lymphoblastoid IFN (6 × 104 units/ml). After exposure of A 549 cells to the three IFNs at these concentrations, no significant alteration of the ability of the cells to attach to the basement membrane was found. Moreover, none of the one day IFN treatment regimens were cytocidal, and cell proliferation ability was not affected. This model system may be useful for investigating anti-invasive activity of other IFN types and subtypes.