Reversal of Imatinib resistance in BCR-ABL-positive leukemia after inhibition of the Na+/H+ exchanger

被引：19

作者：

Jin, Weina ^{[1
,2
,3
]}

Li, Qinghua ^{[1
,2
,3
]}

Lin, Yani ^{[1
,2
,3
]}

Lu, Ying ^{[1
,2
,3
]}

Li, Huawen ^{[1
,2
,3
]}

Wang, Lihong ^{[1
,2
,3
]}

Hu, Ronghua ^{[1
,2
,3
]}

Ma, Li ^{[1
,2
,3
]}

Wang, Jianxiang ^{[1
,2
,3
]}

Pang, Tianxiang ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China

[2] Chinese Acad Med Sci, Hosp Blood Dis, Tianjin 300020, Peoples R China

[3] Peking Union Med Coll, Tianjin 300020, Peoples R China

来源：

CANCER LETTERS | 2011年 / 308卷 / 01期

关键词：

BCR-ABL; P-glycoprotein; Na+/H+ exchanger 1; Intracellular pH; Mitogen-activated protein kinase; CHRONIC MYELOGENOUS LEUKEMIA; JUN NH2-TERMINAL KINASE; BREAST-CANCER CELLS; P-GLYCOPROTEIN; C-JUN; SIGNAL-TRANSDUCTION; DOWN-REGULATION; EXPRESSION; PATHWAY; OVEREXPRESSION;

D O I：

10.1016/j.canlet.2011.04.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 (pH(i)), 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

引用

页码：81 / 90

页数：10

共 27 条

[1] The functional contrariety of JNK [J].