Drug concentration-dependent expression of multidrug resistance-associatedprotein and P-glycoprotein in the doxorubicin-resistant acute myelogenous leukemia sublines

The multidrug resistance of cancer cells can be mediated by an overexpressi on of the human MDR1 and MRP genes, which encode the transmembrane efflux p umps, the 170 kDa P-glycoprotein (Pgp) and the 190 kDa multidrug resistance -associated protein (MRP), respectively. In this study, we investigate whic h protein is preferentially overexpressed in the function of doxorubicin co ncentrations in the acute myelogenous leukemia cell line (OCI/AML-2). Multi drug-resistant AML-2 sublines were isolated in doxorubicin concentrations o f 20, 100, 250, and 500 ng/ml, MRP was at first expressed at low concentrat ions of less than 5 x IC50 (100 ng/ml) of doxorubicin followed by the overe xpression of Pgp with concentrations of more than 12.5x IC50 (250 ng/ml) of doxorubicin, In addition, it appeared that increased amounts of MRP and it s mRNA in AML-2/DX20 and /DX100 decreased gradually in both AML-2/DX250 and /DX500 overexpressing Pgp, In conclusion, it is thought that the overexpre ssion of MRP or Pgp is dependent upon drug concentrations. It could be impl icated that the overexpression of MRP might be negatively related to that o f Pgp.