Abstract:

Objective
To observe the effect of nuclear factor kappa B (NF-κB) and multi-drug resistance gene MDR1 on leukemia chemotherapy resistance,to demonstrate the relationship between  NF-κB and multidrug-resistance and the related mechanism.Methods  Erythroleukemia cells K562 and adriamycin(ADM)-resistance cells K562/ADM were treated with  ADM (0,0.25,0.50,1.00,2.00   μg·L^-1) or mitomycin (MIT)(0,2,4,8,16 mg·L^-1)　for 48 h. The cell viability was detected by MTT assay,the cell resistant factor was calculated,MDR1 and IκB mRNA levels were detected by RT-PCR;P-gp and  P65 protein levels were detected by Western blotting.
Results Compared with control group,0.50 and 1.00   μg·L^-1 ADM or 4 and 8 mg·L^-1  MIT inhibited the cell viability significantly in erythroleukemia cells K562 in a dose-dependent manner (P<0.01);but had no significant effect on drug-resistance cells;on the mRNA level,compared with K562 cells,the  expression level of MDR1 mRNA in K562/ADM cells was higher(P<0.01).Compared with control group,the expressions of  IκBα mRNA decreased(P<0.01)　 in K562 cells or K562/ADM cells treated with  0.50 and 1.00   μg·L^-1 ADM  or 4 and 8 mg·L^-1　 MIT respectively in a dose-dependent manner.On the protein level,compared with K562 cells,the expression of P-gp protein increased(P<0.01)；compared with control group,the expression of P-gp protein  increased (P<0.01),the expression of P65 protein increased at the same time  in a  dose-dependent manner in K562/ADM cells treated with 0.50 and 1.00 μg·L^-1 ADM or 4 and 8 mg·L^-1 MIT(P<0.01).Conclusion The high  expression of MDR1 gene and P-gp protein may be the essential mechanism of drug resistance in K562 cells,and the activation of NF-κB may be involved in the regulation of multi-drug resistance.

Key words: multi-drug resistance gene;nuclear factor κB；P65