Skip to main content
. Author manuscript; available in PMC: 2020 Jan 1.
Published in final edited form as: Cancer Lett. 2018 Oct 9;440-441:1–10. doi: 10.1016/j.canlet.2018.10.003

Figure 5. Pan-PIM kinase inhibitors up-regulate CRBN and promote the degradation of IKZF1 and IKZF3.

Figure 5.

A. SGI176 (10µM) and CX6258 (5µM) upregulated CRBN mRNA expression. B. SGI176 (10µM) and CX6258 (5µM) increased CRBN protein expression level and down-regulated protein expression of IKZF1, IKZF3, c-Myc and IRF4 measured at 24h after treatment. C. MM1R cells were transduced with lentiviral vector encoding control shRNA (shCTR) or CRBN-specific shRNA (shCRBN) lentivirus for 48h and CRBN mRNA expression was measured by real-time PCR. D. IKZF1 and IKZF3 protein expression was measured after sh CRBN or sh CTR lentivirus infections. E. Knockdown of CRBN significantly reduced the anti-myeloma effects of pan-PIM kinase inhibitors. MM1R cells were transduced with lentiviral vector encoding control shRNA (shCTR) or CRBN-specific shRNA (shCRBN) lentivirus for 48h and treated with SGI1776 (10µM) and CX6258 (5µM). Annexin V+ cells were measured by flow cytometry. Percentages of Annexin V+ cells from 3 separate sets of experiments were shown (Mean ± SEM). F. The survival of the mice treated with SGI1776 and lenalidomide combination was almost the same as that of the mice treated with SGI1776 alone. At day 29 after cell injection, transplanted VK*MYC myeloma mice were treated with either: DMSO, SGI1776 alone, lenalidomide alone, or the combination of SGI1776 and lenalidomide. (ns: no statistically significant; *: p<0.05; **: p< 0.01; ***:p<0.001)