- Jianan Pang1,
- Qiaofa Shi2,
- Zhiqiang Liu2,
- Jin He2,
- Huan Liu2,
- Pei Lin3,
- Jiuwei Cui1 and
- Jing Yang2,*
- 1 The First Hospital of Jilin University, Changchun, Jilin Province, China;
- 2 Dept of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, USA;
- 3 Dept of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, USA
- ↵* Corresponding author; email:
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 chemotherapy resistance 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 which is secreted from adipocytes, in myeloma chemotherapy resistance. 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 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, and targeting resistin implicates a potential strategy to prevent or overcome multidrug resistance in myeloma.
- Received August 8, 2016.
- Accepted March 23, 2017.
- Copyright © 2017, Ferrata Storti Foundation