Inhibition of c-Myc overcomes cytotoxic drug resistance in acute myeloid leukemia cells by promoting differentiation.
Inhibition of c-Myc overcomes cytotoxic drug resistance in acute myeloid leukemia cells by promoting differentiation.
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DOI：
10.1371/journal.pone.0105381
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Lin DJ
中科院分区：
文献类型：
--
作者：
Pan XN;Chen JJ;Wang LX;Xiao RZ;Liu LL;Fang ZG;Liu Q;Long ZJ;Lin DJ
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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影响因子：
5.2
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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影响因子：
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DOI：
10.1016/j.bbrc.2012.07.098
发表时间：
2012-08-24
影响因子：
3.1
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通讯作者：
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