Resistin induces multidrug resistance in myeloma by inhibiting cell death and upregulating ABC transporter expression.
Resistin induces multidrug resistance in myeloma by inhibiting cell death and upregulating ABC transporter expression.
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抵抗素通过抑制细胞死亡和上调ABC转运蛋白表达来诱导骨髓瘤的多药耐药性。
DOI：
10.3324/haematol.2016.154062
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发表时间：
2017-07
期刊：
影响因子：
10.1
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Pang J;Shi Q;Liu Z;He J;Liu H;Lin P;Cui J;Yang J
Despite advances in therapy, multiple myeloma remains incurable, with a high frequency of relapse. This suggests the need to identify additional factors that contribute to drug resistance. Our previous studies revealed that bone marrow adipocytes promote resistance to chemotherapy in myeloma through adipocyte-secreted adipokines, but the mechanism underlying this effect and the specific adipokines involved are not well understood. We proposed to determine the role of resistin, an adipokine that is secreted by adipocytes, in chemotherapy resistance in myeloma. We found that resistin abrogated chemotherapy-induced apoptosis in established myeloma cell lines and primary myeloma samples. Resistin inhibited chemotherapy-induced caspase cleavage through the NF-κB and PI3K/Akt pathways. Resistin also increased the expression and drug efflux function of ATP-binding cassette (ABC) transporters in myeloma cells through decreasing the expression of both DNA methyltransferases DNMT1 and DNMT3a and the methylation levels of ABC gene promoters. In vivo studies further demonstrated the protective effect of resistin in chemotherapy-induced apoptosis. Our study thus reveals a new biological function of resistin in the pathogenesis of myeloma, with the implication that targeting resistin could be a potential strategy to prevent or overcome multidrug resistance in myeloma.
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