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Inhibition of c-Myc Overcomes Cytotoxic Drug Resistance in Acute Myeloid Leukemia Cells by Promoting Differentiation

Nowadays, drug resistance still represents a major obstacle to successful acute myeloid leukemia (AML) treatment and the underlying mechanism is not fully elucidated. Here, we found that high expression of c-Myc was one of the cytogenetic characteristics in the drug-resistant leukemic cells. c-Myc o...

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Autores principales: Pan, Xiao-Na, Chen, Jia-Jie, Wang, Le-Xun, Xiao, Ruo-Zhi, Liu, Ling-Ling, Fang, Zhi-Gang, Liu, Quentin, Long, Zi-Jie, Lin, Dong-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134294/
https://www.ncbi.nlm.nih.gov/pubmed/25127121
http://dx.doi.org/10.1371/journal.pone.0105381
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author Pan, Xiao-Na
Chen, Jia-Jie
Wang, Le-Xun
Xiao, Ruo-Zhi
Liu, Ling-Ling
Fang, Zhi-Gang
Liu, Quentin
Long, Zi-Jie
Lin, Dong-Jun
author_facet Pan, Xiao-Na
Chen, Jia-Jie
Wang, Le-Xun
Xiao, Ruo-Zhi
Liu, Ling-Ling
Fang, Zhi-Gang
Liu, Quentin
Long, Zi-Jie
Lin, Dong-Jun
author_sort Pan, Xiao-Na
collection PubMed
description Nowadays, drug resistance still represents a major obstacle to successful acute myeloid leukemia (AML) treatment and the underlying mechanism is not fully elucidated. Here, we found that high expression of c-Myc was one of the cytogenetic characteristics in the drug-resistant leukemic cells. c-Myc over-expression in leukemic cells induced resistance to chemotherapeutic drugs, enhanced colony formation capacity and inhibited cell differentiation induced by all-trans retinoic acid (ATRA). Meanwhile, inhibition of c-Myc by shRNA or specific c-Myc inhibitor 10058-F4 rescued the sensitivity to cytotoxic drugs, restrained the colony formation ability and promoted differentiation. RT-PCR and western blotting analysis showed that down-regulation of C/EBPβ contributed to the poor differentiation state of leukemic cells induced by c-Myc over-expression. Importantly, over-expression of C/EBPβ could reverse c-Myc induced drug resistance. In primary AML cells, the c-Myc expression was negatively correlated with C/EBPβ. 10058-F4, displayed anti-proliferative activity and increased cellular differentiation with up-regulation of C/EBPβ in primary AML cells. Thus, our study indicated that c-Myc could be a novel target to overcome drug resistance, providing a new approach in AML therapy.
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spelling pubmed-41342942014-08-19 Inhibition of c-Myc Overcomes Cytotoxic Drug Resistance in Acute Myeloid Leukemia Cells by Promoting Differentiation Pan, Xiao-Na Chen, Jia-Jie Wang, Le-Xun Xiao, Ruo-Zhi Liu, Ling-Ling Fang, Zhi-Gang Liu, Quentin Long, Zi-Jie Lin, Dong-Jun PLoS One Research Article Nowadays, drug resistance still represents a major obstacle to successful acute myeloid leukemia (AML) treatment and the underlying mechanism is not fully elucidated. Here, we found that high expression of c-Myc was one of the cytogenetic characteristics in the drug-resistant leukemic cells. c-Myc over-expression in leukemic cells induced resistance to chemotherapeutic drugs, enhanced colony formation capacity and inhibited cell differentiation induced by all-trans retinoic acid (ATRA). Meanwhile, inhibition of c-Myc by shRNA or specific c-Myc inhibitor 10058-F4 rescued the sensitivity to cytotoxic drugs, restrained the colony formation ability and promoted differentiation. RT-PCR and western blotting analysis showed that down-regulation of C/EBPβ contributed to the poor differentiation state of leukemic cells induced by c-Myc over-expression. Importantly, over-expression of C/EBPβ could reverse c-Myc induced drug resistance. In primary AML cells, the c-Myc expression was negatively correlated with C/EBPβ. 10058-F4, displayed anti-proliferative activity and increased cellular differentiation with up-regulation of C/EBPβ in primary AML cells. Thus, our study indicated that c-Myc could be a novel target to overcome drug resistance, providing a new approach in AML therapy. Public Library of Science 2014-08-15 /pmc/articles/PMC4134294/ /pubmed/25127121 http://dx.doi.org/10.1371/journal.pone.0105381 Text en © 2014 Pan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pan, Xiao-Na
Chen, Jia-Jie
Wang, Le-Xun
Xiao, Ruo-Zhi
Liu, Ling-Ling
Fang, Zhi-Gang
Liu, Quentin
Long, Zi-Jie
Lin, Dong-Jun
Inhibition of c-Myc Overcomes Cytotoxic Drug Resistance in Acute Myeloid Leukemia Cells by Promoting Differentiation
title Inhibition of c-Myc Overcomes Cytotoxic Drug Resistance in Acute Myeloid Leukemia Cells by Promoting Differentiation
title_full Inhibition of c-Myc Overcomes Cytotoxic Drug Resistance in Acute Myeloid Leukemia Cells by Promoting Differentiation
title_fullStr Inhibition of c-Myc Overcomes Cytotoxic Drug Resistance in Acute Myeloid Leukemia Cells by Promoting Differentiation
title_full_unstemmed Inhibition of c-Myc Overcomes Cytotoxic Drug Resistance in Acute Myeloid Leukemia Cells by Promoting Differentiation
title_short Inhibition of c-Myc Overcomes Cytotoxic Drug Resistance in Acute Myeloid Leukemia Cells by Promoting Differentiation
title_sort inhibition of c-myc overcomes cytotoxic drug resistance in acute myeloid leukemia cells by promoting differentiation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134294/
https://www.ncbi.nlm.nih.gov/pubmed/25127121
http://dx.doi.org/10.1371/journal.pone.0105381
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