Modulation of cisplatin sensitivity and accumulation by interferon α‐2A in human squamous carcinoma cell lines

This study was undertaken to elucidate the mechanism(s) of potentiation of cisplatin (CDDP) cytotoxicity by interferon α‐2a (IFN α‐2a) in human squamous carcinoma cell lines SCC‐25 and SCC‐4. IFN α‐2a treatment significantly increased the cytotoxicity of CDDP in both cell lines in a dose‐dependent manner. In SCC‐25 cells, the cytotoxicity of CDDP was increased by about 2‐ and 4‐fold, respectively, by treating the cells with 400 and 800 1U/ml IFN α‐2a. Sensitivity of SCC‐4 cells to CDDP was increased by about 3‐ and 7‐fold, respectively, by 400 and 800 1U/ml IFN α‐2a treatment. Drug uptake experiments revealed approximately 1.4‐ to 5‐fold higher platinum accumulation in IFN α‐2a‐treated cells as compared to respective controls. Cellular levels of glutathione (GSH) and GSH transferase, which have been suggested to be important determinants of tumor cell sensitivity to CDDP, were not altered by IFN α‐2a treatment in either of the cell lines. Northern blot analysis showed a moderate increase (about 30–40%) in the level of MT‐II_A mRNA by IFN α‐2a treatment in these cells. Our results suggest that IFN α‐2a‐mediated sensitization of SCC‐25 and SCC‐4 cell lines to CDDP in vitro may be due to an increase in intracellular platinum accumulation.