Resistance of human multidrug-resistant neoplastic cell lines to paclitaxel-induced-radiosensitization is reduced by the non-immunosuppressive cyclosporine analog SDZ PSC 833.

Abstract

The non-immunosuppressive cyclosporine analog SDZ PSC 833 abolished the resistance of human multidrug resistant (MDR-1, P-gp) human promyelocyte leukemia HL-60/VCR cells in vitro to paclitaxel-induced cell cycle- and viability alterations, as well as resistance to paclitaxel-induced radiosensitization. Furthermore, SDZ PSC 833 abolished also the resistance of human multidrug-resistant ovarian A2780/ADR cells to paclitaxel-induced cell cycle alterations and reduced its resistance to paclitaxel-induced radiosensitization. In these multidrug-resistant ovarian carcinoma cells the supra-additive interaction between paclitaxel and SDZ PSC 833 pre-exposure and subsequent irradiation appeared at slightly higher paclitaxel concentrations (40-100 nM) compared to those required for a similar interaction in the parental drug sensitive A2780 cells (40-80 nM paclitaxel).