Author/Authors :
Jin، نويسنده , , Weina and Li، نويسنده , , Qinghua and Lin، نويسنده , , Yani and Lü، نويسنده , , Ying and Li، نويسنده , , Huawen and Wang، نويسنده , , Lihong and Hu، نويسنده , , Ronghua and Ma، نويسنده , , Li and Wang، نويسنده , , Jianxiang and Pang، نويسنده , , Tianxiang، نويسنده ,
Abstract :
The present study was undertaken to estimate the therapeutic benefit to down-regulate the Na+/H+ exchanger 1 (NHE1) for reversing chemoresistance of BCR-ABL-positive leukemia patient cells and cell lines. As a result, after treatment with specific NHE1 inhibitor Cariporide or high K+ buffer to decrease intracellular pH (pHi), cells from relapsed patients exhibited decreased Pgp level, enhanced Rhodamine123 and drug accumulation, decreased colony-forming ability and the modulations of mitogen-activated protein kinases (MAPKs) activities. Furthermore, we used BCR-ABL-positive cell line K562 and its resistant counterparts K562/DOX and K562/G01 cell lines for further study. Together, these findings suggest that Pgp may be associated with the reversal of drug resistance in BCR-ABL-positive leukemia patients and cell lines by the inhibition of NHE1 though MAPK pathways.
Keywords :
intracellular pH , mitogen-activated protein kinase , BCR-ABL , Na+/H+ exchanger 1 , P-GLYCOPROTEIN
