MALT1 inhibition inhibits cell growth of MM cells ex vivo and in vivo. (A) RPMI8226, H929, and IM9 cells were treated with Mi-2 (0.5 and 1 μM) for 48 hours. Cell cycle was evaluated by flow-cytometric analysis after EdU incorporation. Percentages of cells in G1 phase were calculated and compared among the groups. (B) IM9 and RPMI8226 cells were treated with Mi-2 (0.75 μM). Colony formation assay was performed to evaluate the clonogeneic ability after Mi-2 treatment. The representative figure of IM9 cells is shown (left), and the number of colonies is shown in bar graph (right). (C) IM9, H929, and RPMI8226 cells were treated with different concentration of Mi-2 for 48 hours, and apoptotic cell death was analyzed by flow-cytometric analysis staining with Annexin V/PI. The bar graph shows the ratio of apoptotic death cell. (D) IM9 and H929 cells were treated with indicated concentrations of Mi-2. The caspase-9 and caspase-3/7 activity was assessed by a luminescent assay after MI-2 treatment. The bar graph shows the fold change (FC) of caspase activity compared with dimethyl sulfoxide (DMSO). (E-F) RPMI8226, H929, and IM9 cells were treated with Mi-2 under the conditions indicated. WB assay was used to evaluate the expression of cleaved-caspase 9, cleaved-caspase 3, PARP, Bcl2, Bax, p21, and p27 proteins. GAPDH was used as a loading control. (G) RPMI8226, H929, and IM9 cells were treated with indicated concentrations of Mi-2 in the absence or presence of HS-5 conditional medium for 48 hours. Cell viability was measured by CCK-8 assay. (H) CD138+ primary MM cells from patients with MM were cultured with the indicated concentrations of Mi-2 for 48 hours. Cell viability was assessed by CCK-8 assay. (I) Primary normal hematopoietic cells were treated with the indicated concentrations of Mi-2 for 48 hours. Cell viability was assessed by CCK-8 assay. (J) NSG mice injected subcutaneously with RPMI8226 cells were treated with Mi-2 (placebo, 25 mg/kg, 5 days per week) intraperitoneally for 4 weeks. The survival of mice was analyzed by Kaplan-Meier survival curves. HR, 0.2785; 95% CI, 0.08-0.98. ns, P > .05; ∗P < .05; ∗∗P < .005; ∗∗∗P < .001; and ∗∗∗∗P < .0001.

MALT1 inhibition inhibits cell growth of MM cells ex vivo and in vivo. (A) RPMI8226, H929, and IM9 cells were treated with Mi-2 (0.5 and 1 μM) for 48 hours. Cell cycle was evaluated by flow-cytometric analysis after EdU incorporation. Percentages of cells in G1 phase were calculated and compared among the groups. (B) IM9 and RPMI8226 cells were treated with Mi-2 (0.75 μM). Colony formation assay was performed to evaluate the clonogeneic ability after Mi-2 treatment. The representative figure of IM9 cells is shown (left), and the number of colonies is shown in bar graph (right). (C) IM9, H929, and RPMI8226 cells were treated with different concentration of Mi-2 for 48 hours, and apoptotic cell death was analyzed by flow-cytometric analysis staining with Annexin V/PI. The bar graph shows the ratio of apoptotic death cell. (D) IM9 and H929 cells were treated with indicated concentrations of Mi-2. The caspase-9 and caspase-3/7 activity was assessed by a luminescent assay after MI-2 treatment. The bar graph shows the fold change (FC) of caspase activity compared with dimethyl sulfoxide (DMSO). (E-F) RPMI8226, H929, and IM9 cells were treated with Mi-2 under the conditions indicated. WB assay was used to evaluate the expression of cleaved-caspase 9, cleaved-caspase 3, PARP, Bcl2, Bax, p21, and p27 proteins. GAPDH was used as a loading control. (G) RPMI8226, H929, and IM9 cells were treated with indicated concentrations of Mi-2 in the absence or presence of HS-5 conditional medium for 48 hours. Cell viability was measured by CCK-8 assay. (H) CD138+ primary MM cells from patients with MM were cultured with the indicated concentrations of Mi-2 for 48 hours. Cell viability was assessed by CCK-8 assay. (I) Primary normal hematopoietic cells were treated with the indicated concentrations of Mi-2 for 48 hours. Cell viability was assessed by CCK-8 assay. (J) NSG mice injected subcutaneously with RPMI8226 cells were treated with Mi-2 (placebo, 25 mg/kg, 5 days per week) intraperitoneally for 4 weeks. The survival of mice was analyzed by Kaplan-Meier survival curves. HR, 0.2785; 95% CI, 0.08-0.98. ns, P > .05; ∗P < .05; ∗∗P < .005; ∗∗∗P < .001; and ∗∗∗∗P < .0001.

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