Sensitivities of human glioma cell lines to interferons and double-stranded RNAs individually and in synergistic combinations

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Abstract
The antiproliferative effects of human interferons (IFNs) and double-stranded RNAs (dsRNAs) were studied in five human glioma cell lines. Dose response curves were generated over a 72 hour treatment period. The concentration of interferon or double-stranded RNA necessary to produce a 50% antiproliferative response (GI50) was calculated by linear regression analysis. Two cell lines were more sensitive to IFN-β than to IFN-α, one cell line was more sensitive to IFN-α than to IFN-β and two cell lines had approximately equal sensitivities to both interferons. All cell lines showed some sensitivity to either IFN-α or IFN-β. IFN-γ had no antiproliferative effect on any of the cell lines. In addition, only one of the cell lines displayed sensitivity to dsRNA, in which the response to poly(I) · poly(C) was greater than that to a mismatched analogue of poly(I) · poly(C), r(I)n · r(C12,U)n (Ampligen). There was no correlation between the sensitivities to type I IFNs (α and β), type II IFN (γ) or the dsRNAs. The antiproliferative effect of combinations of IFNs, or IFNs and Ampligen, was studied in one of the cell lines. A significant synergistic antitumor effect was seen with all of the IFN/Ampligen combinations (p < 0.02), including IFN-γ/Ampligen, even though these cells were resistant to IFN-γ alone. Synergy was also seen in the IFN-α/IFN-γ (p < 0.02) and IFN-β/IFN-γ (p < 0.05) combinations. The IFN-α/IFN-β combination gave an additive antitumor effect. These results indicate that IFN-α and IFN-β alone or combinations of type I IFNs, type II IFNs and Ampligen can be effective in inhibiting the growth of glioma cells.