Synergistic inhibition effect of TNIK inhibitor KY-05009 and receptor tyrosine kinase inhibitor dovitinib on IL-6-induced proliferation and Wnt signaling pathway in human multiple myeloma cells
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Yura Lee1,4, Jung-Il Jung1, Kyeong-Yong Park2, Soon Ae Kim3 and Jiyeon Kim1
1Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon 34824, Korea
2R&D Center, Peptron, Inc., Daejeon 34054, Korea
3Department of Pharmacology, School of Medicine, Eulji University, Daejeon 34824, Korea
4Present address: Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, College of Medicine, Yonsei University, Seoul 03722, Korea
Jiyeon Kim, email: email@example.com
Keywords: multiple myeloma, TNIK, KY-05009, IL-6, Wnt signaling
Received: December 06, 2016 Accepted: March 21, 2017 Published: April 12, 2017
Multiple myeloma is a fetal form of plasma cell malignancy characterized by abnormal clonal proliferation of plasma cells. Especially, the canonical Wnt signaling pathway mediated by β-catenin is activated in multiple myeloma cells, stimulating their proliferation. Here, we investigated the relationship between interleukin-6-induced proliferation of multiple myeloma cells and Traf2- and Nck-interacting kinase (TNIK) expression in Wnt signaling. Interleukin-6 increased the proliferation of multiple myeloma cells and TNIK mRNA and protein expression. In addition, we examined the effect on TNIK of TNIK inhibitor KY-05009 and receptor tyrosine kinase inhibitor dovitinib and whether inhibition of TNIK suppresses the interleukin-6-induced proliferation of multiple myeloma cells. KY-05009 and dovitinib synergistically inhibited interleukin-6-stimulated proliferation and induced apoptosis through the inhibition of Wnt signaling in MM cells. Our results provide crucial information that TNIK is involved in the interleukin-6-dependent proliferation of multiple myeloma cells and inhibition of Wnt signaling involving TNIK could be a therapeutic strategy for the treatment of interleukin-6-dependent multiple myeloma.
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