Effect Of Cyclosporine A And Estrogen-receptor Inhibitor On The Reversion Of Multidrug Resistance Of K562/A02 Line

Objective: This paper was to study the reverl effect of cyclosporine A and the estrogen-receptor inhibitor, raloxifene, on multidrug resistance cell line K562/A02 and to investigate the reversal mechanism of this combination, and to provide theoretic evidence for the clinical application of them as resistance modifying agents.Method: The IC50 (the concentration causing 50% inhibition of cell growth) of DNR were assayed by MTT method; mdr1 mRNA was assayed by RT-PCR.;intracellular drug concentration and the apoptosis was measured by fluorometry;and p-glycoprotein expression was detected by fluorometry .Results: The IC50 of DNR for K562/A02 and K562 cells were 23.51mg/L and0.29mg/L respectively. Pretreating K562/A02 cells with raloxifene(2.5mg/L)or CsA( 1mg/L) for 48 hours partially restored the sensitivity of K562/A02 cells to DNR (IC50 were5.98mg/L and 8.15mg/L respectively) but had no effect on K562 cells; IC50 of combined cyclosporine A and raloxifene was 3.68mg/L;K562/A02 showed apoptotic characteristics after treated with cyclosporine A ;cyclosporine A and raloxifene (alone or combination) elevated the intracellular DNR accumulation in K562/A02 ; p-gp and mdr1 mRNA were down regulated. Data was analyzed by SPSS 11.0 software and expressed as mean±SD.Conclusions: (1) Activation of P-gp may be involved in the mechanism of MDR of K562/A02 cell line;(2)Multidrug resistance (MDR) can be partially reversed by CsA or raloxifene , of which the combination shows a great synergistic reversal effect.