The antiproliferative effect of human interferons (IFNs) and double-stranded RNAs (dsRNAs) was measured in eight human tumor cell lines, five of which were derived from carcinomas of the bladder. Dose-response curves were generated for a 72-hr treatment period. The concentration of interferon or dsRNA necessary to inhibit tumor cell growth 50% compared to untreated cells was generated by linear regression analysis of the dose-response data. In the seven of eight cell lines in which a direct comparison could be made, IFN-β was a more potent inhibitor than IFN-α. Polyriboinosinic acid·polyribocytidylic acid consistently gave an increased antiproliferative response compared to its mismatched analogue, rln·r(C12,U)n. Correlations could not be made between either IFN-α or IFN-β and the dsRNA effect. No correlation was seen between IFN or dsRNA sensitivity and cell type, ability to bind IFN, growth rate, or tumorigenicity in nude mice.
The antiproliferative effect of dsRNA was studied in the presence of antibodies against IFN-β in HT1080 Cl 4, a cell line sensitive to both IFN and dsRNA, and A2182, a cell line relatively resistant to IFN-β but sensitive to dsRNA. In both cell lines, the anti-IFN-β antibodies inhibited the antiproliferative effect of the dsRNAs. After treatment with a concentration of dsRNA necessary to inhibit tumor cell growth 50% compared to untreated cells, a concentration of IFN-β necessary to inhibit tumor cell growth 50% was induced in the HT1080 Cl 4 cells; however, only a low level of IFN-β was detected in the culture medium of the A2182 cells.
This work was supported in part by USPHS Grant P01 CA-29545 from the National Cancer Institute and by the Interferon Research Fund through M. D. Anderson Hospital and Tumor Institute.