Fig. 4.
Bortezomib or MLN4924 potentiates IMiDs-induced MM cell cytotoxicity by inhibiting SCFFbox7 -mediated degradation of CRBN. a Immunoblot analysis of IKZF3 and CRBN levels in CSN6 knockout MM.1S cells. Cells were treated with Poma (P, 10 nM) for 4 h after incubating with bortezomib (B, 5 nM) for 24 h or DMSO (d) (left panel). Proliferation of CSN6 knockout MM.1S cells treated with Poma (20 nM) for 5 days after incubating with or bortezomib (1.5 nM) or DMSO for 24 h. Error bars represent s.e.m. (n = 3) (right panel). b Proliferation of MM.1S or OPM2 cells treated with Lena (10 nM) for 5 days after incubating with bortezomib (1.5 nM) or DMSO for 24 h. Error bars represent s.e.m. (n = 3). c Cell viability of MM.1S cells treated with indicated concentrations of Poma for 3 days after incubating with MLN4924 (0.2 μM) for 36 h. Error bars represent s.e.m. (n = 3) (left panel). Immunoblot analysis of IKZF1/3 and CRBN levels in MM.1S cells treated with Poma (P, 10 nM) for 16 h, after incubating with MLN4924 (M, 0.2 μM) or DMSO (d) for 48 h (right panel)