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

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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-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.

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  1. Howard R. Hubbell

    Present address: Department of Neoplastic Diseases, Hahnemann University, Broad and Vine Streets, 19102, Philadelphia, PA, USA

Authors and Affiliations

  1. Department of Neoplastic Diseases, Hahnemann University, Broad and Vine Streets, 19102, Philadelphia, PA, USA

    Howard R. Hubbell

  2. Department of Medicine, Rochester General Hospital, 1425 Portland Avenue, 14621, Rochester, New York, USA

    Robbin S. Dick

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Dick, R.S., Hubbell, H.R. Sensitivities of human glioma cell lines to interferons and double-stranded RNAs individually and in synergistic combinations. J Neuro-Oncol 5, 331–338 (1987). https://doi.org/10.1007/BF00148390

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