کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2182857 | 1095522 | 2015 | 10 صفحه PDF | دانلود رایگان |
Nucleophosmin/B23 (NPM) is a nuclear protein with prosurvival and ribosomal RNA processing functions. However, the potential role of NPM involved in drug-resistance in leukemia has not been investigated clearly. In this study, we generated an adriamycin (ADM)-resistant lymphoblastic cell line Molt-4/ADR (MAR) by stepwise induction. Cell proliferation, sensitivity to chemotherapy agents and expressions of drug resistance related molecules were assessed. The IC50 of Molt-4 cells were 0.58 ± 0.11 μmol/L and MAR cells were 22.56 ± 1.94 μmol/L, meaning MAR cells were 38.63 fold resistant to Molt-4 cells. Furthermore, MAR cells gained an expression of mdr-1 (P-gp) and a higher expression of NPM compared to Molt-4 cells. Knockdown of NPM by RNA interference (RNAi) suppressed the viability of both Molt-4 and MAR cells. After NPM RNAi, the IC50 of MAR and Molt-4 cells were 3.83 ± 0.38 μmol/L and 0.19 ± 0.02 μmol/L respectively. Both of them revealed an increase of drug sensitivity with down-regulation of mdr-1 and Akt/mTOR signaling. Knockdown of mdr-1 could also reverse the drug resistance, with no change in NPM expression. It could be concluded that knockdown of NPM reversed the drug resistance by down-regulating P-gp and Akt/mTOR signal pathway, indicating that NPM may serve as a potential modulator in drug resistance.
Journal: Immunobiology - Volume 220, Issue 3, March 2015, Pages 331–340