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Synergistic Effect of Human Immune Interferon and Double-Stranded RNA against Human Colon Carcinoma Cells in Vitro

Applied Pharmacology Section, Laboratory of Medicinal Chemistry and Pharmacology Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland 20205

The cytocidal activity of human immune interferon (IFN-) in combination with the synthetic double-stranded RNA, poly(I)·poly(C), was investigated in human colon carcinoma cell line HT-29. Three days of treatment with IFN- (10 to 25 units/ml) resulted in 30 to 40% reduction in colony formation, whereas poly(I)·poly(C) (25 to 100 µg/ml) reduced cell viability by 10 to 20% of control. The lethal effect of the combination of IFN- and poly(I)·poly(C) was synergistic wherein 70 to 90% reduction in colony formation was observed. Measurements of DNA, RNA, and protein synthesis after IFN- and poly(I)·poly(C) treatment showed a dose-dependent reduction in all three parameters. Recombinant IFN- in combination with poly(I)·poly(C) exhibited a similar effect. Studies evaluating the molecular mechanism of IFN- and poly(I)·poly(C) toxicity indicate a lack of involvement of the double-stranded RNA-dependent (2',5')oligoadenylate-RNase L and protein kinase pathways; however, the effect appears to be related to the inhibition of ribosomal RNA transcription in this cell line.

¹ To whom requests for reprints should be addressed, at National Cancer Institute, Building 37, Room 5D02, Bethesda, MD 20205.

Received 9/ 6/84. Revised 1/ 8/85. Accepted 3/ 8/85.

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