I3MO suppresses the growth of bortezomib-resistant cell via down-regulating USP7 expression. (a) The level of γ-H2AX was detected by western blots in ARP1, U266, RPMI8226, ANBL6 and ANBL6 BR cells which treated with I3MO (0, 5, 10 μM) for 24 h. (b) Western blots were utilized to detect the levels of p53, p21, BCL-2, p-IKKα/β (Ser176/180), p-p65-S536, USP7 and GAPDH in ARP1, U266, RPMI8226, ANBL6 and ANBL6 BR cells which treated with I3MO for 24 h. (c) The levels of USP7 and NEK2 were evaluated by western blots in ARP1 cell line with EV and NEK2-OE. (d) ARP1 cell line with EV and NEK2-OE cells were treated with I3MO for 24 h, followed by an assessment of cell viability (P<0.01, Two-way ANOVA). (e) OCI-MY5 cell line with EV and NEK2-OE cells were treated with I3MO for 24 h, followed by an assessment of cell viability (P<0.001, Two-way ANOVA). (f) OCI-MY5 cells with EV and NEK2-OE cells were treated with or without I3MO for 24 h, and cytosolic and nuclear fractionation was carried out. The levels of NEK2 and p65 were analyzed by western blots. GAPDH or Histone H3 (H3) was used as cytosolic and nuclear markers, respectively. The experiments were performed in triplicate. **P < 0.01; ***P < 0.001.