Abstract
We evaluated the effect of PSC-833 a cyclosporine derivative for its MDR1 reversing activity on vincristine and adriamycin resistance in human neuroblastoma cell lines. The cell lines have high, intermittent and low MDR1 expression. Resistance to vincristine and adriamycin was inverse to the degree of MDR1 expression. Resistance could be lowered with longer exposures to drug in all three cell lines. PSC-833 was able to reverse resistance in the SK-N-FI cells to a greater degree than in the two cell lines with lower expression of MDR1. These data suggest that MDR1 may play a protective role against vincristine and adriamycin in human neuroblastoma cells, and PSC-833 can reverse this protection. The duration of exposure to drug alters the response and the effect of PSC-833 on reversal of resistance. Where MDR1 is minimally expressed, PSC-833 is ineffective. Overall activity of vincristine and its modulation by PSC-833 were more consistent than that of adriamycin. Multiple drug resistance mechanisms are complex and vary among different cell lines when challenged with MDR1 drugs and reversing agents.
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