Chemotherapy Sensitization To THP-1 Cells And Relationship With Multidrug Resistance Associated Protein-1 Treated By Cyclosporin A

Acute Monocytic Leukemia is one type of Acute Myeloid Leukemia,which blongs to high incidence,multidrug-resistance and poor prognosis.According to the most related studies,multidrug resistance associated protein-1(MRP1) becomes the main element to make up the multidrug-resistance,which can prevent daunorubicin(DNR) from enter into cells. cyclosporin A (CsA) can reverse drug-resistance of p-glycoprotein for chemotherapy sensitization. Till now There have been not only few studies on drug-resistance of MRP1 reversed by CsA,but also no similar study on Acute Monocytic Leukemia's MRP1.This experiment researches on chemotherapy sensitization of THP-1 cells,a classic cell line of Acute Monocytic Leukemia ,treated by CsA and relationship with MRP1,in order to supply some initial experiment basis for improving therapeutic effects of Acute Monocytic Leukemia.Explore CsA's function of chemotherapy sensitization to THP-1 cells as well as the related mechanism in this experiment by observing the changes of resistance to DNR and expression of MRP1 in Acute Monocytic Leukemia cell line THP-1 treated by CsA or not.50% inhibiting concentration (IC50) of DNR to THP-1 cells, content and distribution of DNR in THP-1 cells treated by CsA are examined by MTT method, fluorescence spectrophotometry method and Confocal laser scanning microscopy method, respectively. Expression amount of MRP1 are detected by immunocytochemistry and Western blot in order.The experiment results show that Comparing with Group DNR, IC50 decreases obviously(1.4997±0.2338 & 0.5584±0.0670, P <0.01),content of DNR increasing obviously ( 20.90±2.4975 &126.50±14.7815, P <0.01),DNR distributing more uniformity, and expression of MRP1 increases both on qualitation and quantity(0.2665±0.0042 & 0.3169±0.0062, P <0.01) in Group CsA+DNR.In a word, CsA can increase the sensibility of THP-1 cells to DNR,while expression of MRP1 on THP-1 cells increases, not decreases.The results show that the resistance of THP-1 cells to DNR isn't reduced by decreasing expression amount.