I3MO works as proteasome inhibitor via suppressing PSME3 and PSME4 expression. (a) The chymotrypsin- (CT-L) and (b) caspase-like (C-L) proteasome activity of ARP1, U266 and ANBL6 BR cells were examined after the treatment with I3MO monotherapy or combination therapy (P<0.05, t test). (c) The heatmap showed several genes of protease complex were down-regulated by I3MO induction. (d,e) ARP1, ANBL6 and ANBL6 BR (BTZ-resistant) cells were treated with or without I3MO (5 µM) for 24 h, and the mRNA levels of PSME3 and PSME4 were detected by real time-PCR (P<0.05, t test). (f) Western blots were utilized to detect the levels of PA28γ, PA200 before and after the I3MO treatment. The experiments were performed in triplicate. *P < 0.05; **P < 0.01; ***P < 0.001.