| Objective:Study the reversal effects and mechanisms of mifepristone (MIF)combined with arsenic trioxide (As2O3) on K562/ADM cells. Providing experimental basis for it's clinical application in refractory acute leukemia.MethodsThe cell growth inhibition,cell apoptosis rate,MRP expression level and glutathione content of K562/ADM cells treated with or without MIF, As2O3, MIF combined with As2O3 were treated by methyl thiazolyl tetrazolium salt (MTT) assay,AnnexinV / PI labeling, RT-PCR method, Spectrophotometry detecting .Results1.As2O3 shows no significant inhibitory effect on K562/ADM at the concentration of 1.0umol / L.The inhibitory rate is very small(15.69±3.56%) when at 2.0umol/L, but it shows significant effect in the dose of more than or equal to 4umol/L. The inhibitory effect was in a dose dependent manner,P<0.05.2. MIF shows no significant inhibitory effect on K562/ADM at the concentration varies from 0 to 10umol/L, but shows significant effect in the dose of more than 10umol/L. The inhibitory effect was in a dose dependent manner,P<0.05.3. All the MIF, As2O3 , MIF plus As2O3 can induce drug resistance retroconversion, and the retroconversion index are 2.32, 1.86, 3.92 times respectively. When the concentration of ADM varies from1.25 to 10.0, the inhibitory effect of MIF plus As2O3 is significantly higher than that of the same concentration of single-drug group alone, P<0.05 .4. The apoptosis-inducing effect is caused When MIF is at the concentrations of 10umol/L, the apoptosis rate is 26.38±2.59%.As2O3 shows no significant apoptosis-inducing effect on K562/ADM cells at the concentration of 1.0umol /L.When is at 2.0umol/L,the apoptosis rate is 20.13±3.56%,but shows significant effect in the dose of more than 4.0umol/L.Compared with MIF, As2O3 monotherapy group,it's apoptosis rate is higher significantly,P<0.05 . 5. GSH content of K562 cells is 48.32±9.26g/L, and that of K562/ADM cells is 79.22±4.60g/L, The resistant cells were significantly higher than the sensitive cells P<0.01. GSH content is 53.58±3.17g/L when MIF deals with K562/ADM cells alone,and that of is 53.08±6.02g/L when the United Group.Compared between the two, P>0.5.Compared with the resistant cells without drugs,Two ways are significantly lower,P<0.01.GSH content is 77.05±4.54g/L when As2O3 deals with K562/ADM cells alone,Compared with the resistant cells without drugs, P>0.5, with the United Group,P<0.01.6. The MRP gene expression of K562/ADM cells(0.98±0.11) is higher Significantly than that of K562 cells(0.20±0.07),P<0.01.Compared with MIF, As2O3 monotherapy group,MRPmRNA/β-Action ratio of K562/ADM cells decreased significantly in the united group,P <0.01, Compared with the control group separately, their MRPmRNA/β-Action ratio significantly decreased also,P <0.01.Conclusion1. When As2O3 is at the concentration of 0-2umol/L, the cell proliferation inhibitory is not very clear. But it shows significant inhibitory effect in the dose of more than or equal to 4umol/L.2.When MIF is at the concentration of 0-10umol/L, the cell proliferation inhibitory is not very clear.But it shows significant inhibitory effect in the dose of more than 10umol/L.3. MIF and As2O3 are both can reverse the resistance of K562/ADM cells, the retroconversion effect of MIF combined with As2O3 on K562/ADM cells is stronger.4. MIF and As2O3 are both can induce the apoptosis-inducing effect ,the apoptosis-inducing effect of MIF combined with As2O3 on K562/ADM cells is stronger.5. The GSH content of K562/ADM cells is significantly higher than K562 cells, MIF can significantly reduce GSH content of K562/ADM cells.6. K562/ADM cells has a high expression of MRP,MIF,As2O3 can inhibit MRP expression K562/ADM cells, The inhibitory effect of MIF plus As2O3 is more obvious.7. To MIF combined with As2O3, the retroconversion effect is stronger obviously, it's mechanisms may be related to apoptosis strengthen, reducing GSH content, MRP expression inhibition.
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