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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

Yura Lee, Jung-Il Jung, Kyeong-Yong Park, Soon Ae Kim, Jiyeon Kim

Oncotarget. 2017 Jun 20;8(25):41091-41101.

PMID: 28467797

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP1228280292 KY-05009 KY-05009 1228280-29-2 Price
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