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Published on: January 18, 2017
Visfatin promotes multiple myeloma cell proliferation and inhibits apoptosis by inducing IL-6 production via NF-κB
Wenting Tie1,2, Tao Ma3, Jia Liu1
1Department of Hematology, The Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, China.
Background:
Multiple myeloma (MM) is the second most prevalent hematological malignancy that results in the proliferation of malignant plasma cells and the overproduction of monoclonal immunoglobulin. Visfatin plays an important role in the regulation of apoptosis, oxidative stress, and inflammation; however, to this date, the role of visfatin in multiple myeloma is unclear.
Objective:
To explore the role of visfatin in multiple myeloma and find new targets for MM treatment.
Methods:
In this study, expression of visfatin in bone marrow was detected by ELISA. The diagnostic value of visfatin was determined by receiver operating characteristic (ROC) curve analysis. After the quality control by performing western blot to confirm the knockdown of visfatin in two MM cell lines, the phenotype (proliferation and apoptosis) of visfatin in MM was determined by carrying out in vitro experiments, including CCK8, flow cytometry, and western blot. Several cytokines were determined by real-time PCR, followed by in vivo experiments and immunohistochemical assays. IκB, NF-κbp65, and phosphorylation were determined by western blot.
Results:
We found that visfatin level increased in the bone marrow of MM patients compared to controls. ROC curve analysis result showed that bone marrow visfatin was able to distinguish MM patients from controls. In vitro and in vivo, visfatin promotes MM cell proliferation. The production of IL-6 was attenuated by visfatin knockdown. Furthermore, we showed that visfatin could activate IL-6 production via the NF-κB signaling pathway.
Conclusions:
In MM, visfatin promotes tumor progression by upregulating IL-6 production, which may be a novel therapeutic target for the treatment of MM patients.
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