MODULATION OF CISPLATIN SENSITIVITY AND ACCUMULATION BY INTERFERON ALPHA-2A IN HUMAN SQUAMOUS CARCINOMA CELL-LINES

This study was undertaken to elucidate the mechanism(s) of potentiatio n of cisplatin (CDDP) cytotoxicity by interferon alpha-2a (IFN alpha-2 a) in human squamous carcinoma cell lines SCC-25 and SCC-4. IFN alpha- 2a treatment significantly increased the cytotoxicity of CDDP in both cell lines in a dose-dependent manner. In SCC-25 cells, the cytotoxici ty of CDDP was increased by about 2- and 4-fold, respectively, by trea ting the cells with 400 and 800 IU/ml IFN alpha-2a. Sensitivity of SCC -4 cells to CDDP was increased by about 3- and 7-fold, respectively, b y 400 and 800 IU/ml IFN alpha-2a treatment. Drug uptake experiments re vealed approximately 1.4- to 5-fold higher platinum accumulation in IF N alpha-2a-treated cells as compared to respective controls. Cellular levels of glutathione (GSH) and GSH transferase, which have been sugge sted to be important determinants of tumor cell sensitivity to CDDP, w ere not altered by IFN alpha-2a treatment in either of the cell lines. Northern blot analysis showed a moderate increase (about 30-40%) in t he level of MT-IIA mRNA by IFN alpha-2a treatment in these cells. Our results suggest that IFN alpha-2a-mediated sensitization of SCC-25 and SCC-4 cell lines to CDDP in vitro may be due to an increase in intrac ellular platinum accumulation. (C) 1995 Wiley-Liss, Inc.