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

Summary 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- than to IFN-, one cell line was more sensitive to IFN- than to IFN- and two cell lines had approximately equal sensitivities to both interferons. All cell lines showed some sensitivity to either IFN- or IFN-. IFN- 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 ( and ), type II IFN () 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-/Ampligen, even though these cells were resistant to IFN- alone. Synergy was also seen in the IFN-/IFN- (p < 0.02) and IFN-/IFN- (p < 0.05) combinations. The IFN-/IFN- combination gave an additive antitumor effect. These results indicate that IFN- and IFN- alone or combinations of type I IFNs, type II IFNs and Ampligen can be effective in inhibiting the growth of glioma cells.