Reversion Of Multidrug Resistance By Decitabine And Increasing Concentration Of ADR In K562/ADR Cells

Objective:Leukemia is a malignant turner in hematopoietic system. In recent years, the incidence of the disease has raised ceaseless and treatment is mainly hematopoietic stem cell transplantation (HSCT) and chemotherapy。Hematopoietic stem cell transplantation might be the only way to cure leukemia,but due to the restriction of age as well as suppliers, most leukemia patients cannot be operated hematopoietic stem cell transplantation, whereas chemotherapy will cause drug resistance and relapse。Inactivation of tumor suppressor genes caused by DNA methylation is one of the major mechanisms of tumor。DNA hypermethylation is widespread in malignant hematonosis. Various studies found that DNA methylation can be reversed by drug,but the mechanism of methylation is different from the traditional treatment of chemotherapy and hematopoietic stem cell transplantation, which makes the enhancement of remission rate of the drug resistance as well as relapse leukemia to be possible. DCA is a 2-deoxycytidine analogues, and research has confirmed that the DCA has dual mechanism of anti-tumor activity and gemcitabine in a dose-related, which means it is cytotoxic to cells when high concentration,but has Demethylation when low concentrations。The objective of this study is to observe the reversal effect of Decitabine and Adriamycin on the multidrug resistance of leukemia cell strain K562 and to explore its feasibility to treat leukemia.Methods:K562/ADR cells were treated with different concentrations of Decitabine and ADR 72 hours, and set up comparison group 1 which with DCA only and comparison group 2 which with ADR only.The impact of cell growth curve was observed by Trypan blue staining. Killer acticity of K562/ADR cell with different concentrations of Decitabine & ADR was determined by MTT assay. The concentration of P-glycoprotein in cell membrane and of ADR in cells was determined by FCM. The expression of P151NK4B gene of K562/ADR cell was observed by reverse transcription Polymerase Chain Reaction, RT-PCR. The level of apoptosis of K562/ADR cell was evaluated by DNA electrophoresis.Result:Obvious reversal effects of DCA+ADR on multidrug resistance in leukemia cell strain K562. Decitabine and ADR could decrease the expression of P-glycoprotein as well as enhance the concentration in cell membrane, and could improve the sensibility of multidrug resistant cell strain K562 to ADR. Don't detect the expression of P15INK4B gene but can observe the apoptosis of K562/ADR after using DCA+ADR.Conclusions:1.DCA and ADR could reverse the multidrug resistance on leukemia cell strain K5622. DCA and ADR can enhance the concentration of leukemia cell strain K5623. It may not be P15INK4B gene that is the target of the effect of DCA on leukemia cell strain K562...