期刊
ONCOTARGET
卷 7, 期 18, 页码 26709-26723出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8489
关键词
galectin-1; chronic myelogenous leukemia; chemoresistance; MDR1; P38 MAPK
资金
- National Science Foundation of China [81573334, 81272462]
- Science and Technology Planning Project of Guangdong Province of China [2015A020211017]
- Natural Science Foundation of Zhejiang Province of China [LY14H310013]
- Team Project of Natural Science Foundation of Guangdong Province of China [S2013030013315]
- Guangdong Provincial Thousand-Hundred-Ten Talent Project
Multidrug resistance protein-1 (MDR1) has been proven to be associated with the development of chemoresistance to imatinib (Glivec, STI571) which displays high efficacy in treatment of BCR-ABL-positive chronic myelogenous leukemia (CML). However, the possible mechanisms of MDR1 modulation in the process of the resistance development remain to be defined. Herein, galectin-1 was identified as a candidate modulator of MDR1 by proteomic analysis of a model system of leukemia cell lines with a gradual increase of MDR1 expression and drug resistance. Coincidently, alteration of galectin-1 expression triggers the change of MDR1 expression as well as the resistance to the cytotoxic drugs, suggesting that augment of MDR1 expression engages in galectin-1-mediated chemoresistance. Moreover, we provided the first data showing that NF-kappa B translocation induced by P38 MAPK activation was responsible for the modulation effect of galectin-1 on MDR1 in the chronic myelogenous leukemia cells. Galectin-1 might be considered as a novel target for combined modality therapy for enhancing the efficacy of CML treatment with imatinib.
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