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

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• 作者：Weina Jin^a ; Qinghua Li^a ; Yani Lin^a ; Ying Lu^a ; Huawen Li^a ; Lihong Wang^a ; Ronghua Hu^a ; Li Ma^a ; Jianxiang Wang^a ; Tianxiang Pang ; ^a ; ^{pang@ihcams.ac.cn"" rel=""nofollow}
• 关键词：BCR-ABL ; P-glycoprotein ; Na⁺/H⁺ exchanger 1 ; Intracellular pH ; Mitogen-activated protein kinase
• 刊名：Cancer Letters
• 出版年：2011
• 出版时间：1 September 2011
• 年：2011
• 卷：308
• 期：1
• 页码：81-90
• 全文大小：1664 K

文摘

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.