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. 2021 Apr 10;2(4):370–387. doi: 10.1158/2643-3230.BCD-20-0108

Figure 3.

Figure 3.

JQKD82 suppresses multiple myeloma (MM) cell growth. A, MM.1S cells were cultured with the indicated concentrations of KDM5-C49, KDM5-C70, or JQKD82 for 5 days. Viable cells were determined by MTT assay, and the cell growth relative to untreated control cells is shown. Data represent mean ± SD of triplicate cultures. B, Multiple myeloma cell lines were cultured with the indicated concentrations of JQKD82 for 5 days. Viable cells were determined by MTT assay, and the cell growth relative to untreated control cells is shown. Data represent mean ± SD of triplicate cultures.C, CD138-positive primary multiple myeloma cells were treated with 3 μmol/L of JQKD82 or DMSO for 5 days. The cell viability relative to untreated control was assessed by Cell TiterGlo assay. Data represent mean ± SD of duplicate or triplicate cultures. D, B cells from healthy donors were stimulated by 10 μg/mL of CD40 antibody and 100 U/ml of IL4, and were then treated with JQKD82 for 5 days. The cell growth relative to JQKD82-untreated control was assessed by Cell TiterGlo assay. Data represent mean ± SD of triplicate cultures. E, MM.1S and MOLP-8 cells were incubated with 1 μmol/L of JQKD82 for 48 hours. Cells were fixed, stained with propidium iodide, and analyzed for cell-cycle distribution using flow cytometry. F, MM.1S and MOLP-8 cells were incubated with 1 μmol/L of JQKD82 for 48 to 96 hours. Cells were stained with Annexin V and analyzed for apoptosis using flow cytometry. Data represent mean ± SD of triplicate samples (E and F). *, P < 0.05; **, P < 0.01; ***, P < 0.001 compared with control; unpaired Student t test. G, Schema of in vivo study using a disseminated model. MOLP-8 TurboGFP-Luc cells were intravenously inoculated into NSG mice. After disease establishment confirmed by BLI, the mice were randomized to JQKD82 or vehicle group, and treated i.p. with JQKD82 at 50 mg/kg or vehicle twice a day (BID), respectively, for 3 weeks, and followed for survival. H, Representative BLI of MOLP-8 TurboGFP-Luc cell xenografted mice after treatment with JQKD82 or vehicle control at a dose of 50 mg/kg i.p. twice daily. Images were obtained on day 17 after treatment initiation. Data are representative of nine mice per group. I, Tumor burden was serially evaluated by BLI. Data represent mean ± SEM. n = 9 mice per group. P = 0.028 by comparing treatment group against control group by unpaired Student t test. J, Kaplan–Meier curves showing the survival of JQKD82-treated mice or vehicle control mice. P < 0.0001 by the log-rank test. K, IHC analysis for H3K4me3, Ki67, and MYC in the subcutaneous tumor samples from the MOLP-8 TurboGFP-Luc–injected mice treated with JQKD82 or control. Scale bars, 50 μm. Data are representative of three independent tumors per treatment group.