THE EFFICACY OF 2',2'-DIFLUORODEOXYCYTIDINE (GEMCITABINE) COMBINED WITH INTERFERON IN HUMAN RENAL-CELL CARCINOMA CELL-LINES

The present in vitro study on three human renal cell carcinoma (RCC) c ell lines (A-498, ACHN, SN12C) evaluated the efficacy of 2',2'-difluor odeoxycytidine (dFdC, gemcitabine), vinblastine (VBL), rhu-interferon- alpha (IFN-alpha) and rhu-interferon-gamma (IFN-gamma) alone or in com binations. The cytotoxicity was measured by using the sulphorhodamine B colorimetric cytotoxicity assay. Analyses were made from cells being continuously long-term (greater than or equal to 4 weeks) 'pre-expose d' or short-term (4 h) 'pre-treated' with IFN-alpha or IFN-gamma with regard to the cytotoxicity of the chemotherapeutic agents. dFdC was mo re cytotoxic against ACHN and A-498 cells compared to VBL. Pre-treatme nt with IFN-alpha enhanced growth inhibition caused by dFdC (4/4 cell lines) and VBL (2/3 cell lines), and was more effective than IFN-gamma . Preexposure with IFN-alpha sensitized SN12C and ACHN cells for dFdC. A-498 cells achieved a decreased sensitivity to dFdC and VBL after pr e-exposure to IFN-gamma. The resistance of newly established dFdC-resi stant SN12C cells (23-times) decreased when pre-treated with IFN-alpha . The data demonstrate efficacy of dFdC in human RCC at concentrations below clinically achievable doses. dFdC was more effective compared t o VBL. Combined therapy preferentially with IFN-alpha increased cytoto xicity of dFdC in vitro. In vivo studies in nude mice xenografts are u nder investigation to support these observations.