Choi C H, Kim H S, Rha H S, Jeong J H, Park Y H, Min Y D, Kee K H, Lim D Y
Department of Pharmacology, Chosun University Medical School, Kwangju, Korea.
Mol Cells. 1999 Jun 30;9(3):314-9.
The multidrug resistance of cancer cells can be mediated by an overexpression of the human MDR1 and MRP genes, which encode the transmembrane efflux pumps, the 170 kDa P-glycoprotein (Pgp) and the 190 kDa multidrug resistance-associated protein (MRP), respectively. In this study, we investigate which protein is preferentially overexpressed in the function of doxorubicin concentrations in the acute myelogenous leukemia cell line (OCI/AML-2). Multidrug-resistant AML-2 sublines were isolated in doxorubicin concentrations of 20, 100, 250, and 500 ng/ml. MRP was at first expressed at low concentrations of less than 5 x IC50 (100 ng/ml) of doxorubicin followed by the overexpression of Pgp with concentrations of more than 12.5 x IC50 (250 ng/ml) of doxorubicin. In addition, it appeared that increased amounts of MRP and its 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 overexpression of MRP or Pgp is dependent upon drug concentrations. It could be implicated that the overexpression of MRP might be negatively related to that of Pgp.
癌细胞的多药耐药性可由人类MDR1和MRP基因的过表达介导，这两个基因分别编码跨膜外排泵，即170 kDa的P-糖蛋白（Pgp）和190 kDa的多药耐药相关蛋白（MRP）。在本研究中，我们调查在急性髓性白血病细胞系（OCI/AML-2）中，哪种蛋白在阿霉素浓度作用下优先过表达。在阿霉素浓度为20、100、250和500 ng/ml的条件下分离出多药耐药的AML-2亚系。在阿霉素浓度低于5×IC50（100 ng/ml）时，MRP首先低水平表达，随后在阿霉素浓度高于12.5×IC50（250 ng/ml）时Pgp过表达。此外，在过表达Pgp的AML-2/DX250和/DX500中，AML-2/DX20和/DX100中MRP及其mRNA的增加量逐渐减少。总之，认为MRP或Pgp的过表达取决于药物浓度。可能意味着MRP的过表达可能与Pgp的过表达呈负相关。
