The Effect Of Paeoniflorin On Reversing Multidrug Resistance Of Chronic Myelogenous Leukemia Adriamvcin-resistant K562/ADR Cells And Its Molecular Mechanism

Objective:In this study,the effects of paeoniflorin on multidrug resistance of K562/ADR cells and its molecular mechanism were explored by detecting the fold of resistance of paeonifloin(PF)on human leukemia cell line K562/ADM,the fluorescence intensity of intracellular admiamycin(admiamycin)and the expression of resistance-related protein.It provide theoretical basis for the anti-leukemia effect of paeoniflorin.Methods:Different concentrations of ADR were added to K562 or K562/ADR cells(K562:0.2?0.4?0.8?1.6?g/mL,K562/ADR:16?32?64?128?g/mL).CCK-8 assay was used to detect the fold of resistance to K562/ADR cells.K562/ADR cells were treated with paeoniflorin at different concentrations(2?16?M)for 24 h.The inhibition rate of K562/ADR cells at different concentrations was measured by CCK-8 assay.Then K562/ADR cells were treated with ADR alone or treated with ADR which combine with different concentrations of paeoniflorin(2?M?4?M).The effect of paeoniflorin on cell viability was detected by CCK-8 assay.The cell-associated mean fluorescence intensity of ADR were detected by flow cytometer.The expressions of multidrug resistance-associated protein 1(MRP1)?p38?phosphorylated p38(p-p38)were determined by western blot.Results:The fold of resistance to K562/ADR cells of ADR was 32.91 times,which indicated that K562/ADR cells has stable resistance to ADR compared with sensitive K562 cells.After treated with different concentrations of paeoniflorin(2?16?M)for 24 hours,the growth of K562/ADR cells was inhibited in a dose-dependent manner.Paeoniflorin at non-toxic doses(2?M?4?M)significantly enhanced the cytotoxicity of ADR to K562/ADR cells,and inhibited cell growth,and significantly increased the mean fluorescence intensity of intracellular ADR After treated with different concentrations of paeoniflorin,the expression of MRP 1 and p-p38 protein in K562/ADR cells decreased significantly,while the expression of p38 protein did not change significantly.Conclusions:Paeoniflorin can reverse multidrug resistance of K562/ADR cells in vitro.The mechanism may be related to blocking P38 MAPK signaling pathway,downregulating MRP 1 expressions and increase intracellular accumulation concentrationin of drug.