Objective:To observe the reversion of multi-drug resistance by proteasome inhibitor bortezomib in K562/DNR cell line and to analyze the possible mechanism of reversion of multidrug-resistance.Methods:MTT method was used to determine the drug resistance of K562/DNR cells and the cellular toxicity of bortezomib.K562/DNR cells were cultured for 12 hours,24 hours and 36 hours with 100μg/ml DNR only or plus 4 μg/L bortezomib.The expressions of NF-ΚB,IΚB and P-gp of K562/DNR were detected with Western blot method,the activity of NF-ΚB was tested by ELISA method and the apoptosis rate was observed in each group respectively.Results:The ICso of DNR on cells of K562/S and K562/DNR groups were 1.16μg/ml and 50.43μg/mL,respectively.The drug-resistant fold was 43.47.The IC1O of PS-341 on Cell strain K562/DNR was 4μg/L.Therefore,4μg/L was selected as the concentration for PS-341 to reverse drug-resistance in this study.DNR induced down-regulation of IΚB expression,up-regulation of NF-ΚB and P-gp expression.After treatment with PS-341,a proteasome inhibitor,the IΚB degradation was inhibited,IΚB expression increased,NF-ΚB and P-gp expression decreased in a time dependent manner.Compared to DNR group,the NF-ΚB p65 activity of DNR+PS-341 group was decreased.Compared to corresponding DNR group,DNR induced apoptosis rate increases after addition of PS-341 in a time dependent manner.Conclusion:Proteasome inhibitor bortezomib can convert the leukemia cell drug resistance.The mechanism may be that bortezomib decreases the degradation of IΚB and the expression of NF-ΚB and P-gp,therefore induces the apoptosis of multi-drug resistant cells