The present in vitro study on three human renal cell carcinoma (RCC) cell lines (A-498, ACHN, SN12C) evaluated the efficacy of 2',2'-difluorodeoxycytidine (dFdC, gemcitabine), vinblastine (VBL), rhu-interferon-alpha (IFN-alpha) and rhu-interferon-gamma (IFN-gamma) alone or in combinations. The cytotoxicity was measured by using the sulphorhodamine B colorimetric cytotoxicity assay. Analyses were made from cells being continuously long-term (4 weeks) or short-term (4 h) with IFN-alpha or IFN-gamma with regard to the cytotoxicity of the chemotherapeutic agents. dFdC was more cytotoxic against ACHN and A-498 cells compared to VBL. Pre-treatment 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. Pre-exposure with IFN-alpha sensitized SN12C and ACHN cells for dFdC. A-498 cells achieved a decreased sensitivity to dFdC and VBL after pre-exposure to IFN-gamma. The resistance of newly established dFdC-resistant 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 to VBL. Combined therapy preferentially with IFN-alpha increased cytotoxicity of dFdC in vitro. In vivo studies in nude mice xenografts are under investigation to support these observations.

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