Figure 4.
Low doses of CDDO-Im and bortezomib/proteasome inhibitor PS-341 trigger synergistic anti-MM activity in MM cell lines and patient MM cells. (A) Dex-sensitive (MM.1S) and Dex-resistant (MM.1R) cells were treated with CDDO-Im (80 nM), bortezomib (2 nM), or CDDO-Im + bortezomib for 24 hours and assessed for viability using MTT assays. Results are mean ± SD of 3 independent experiments (P < .006). (B) MM.1S and MM.1R cells were treated with CDDO-Im (80 nM), bortezomib (2 nM), or CDDO-Im + bortezomib for 24 hours; total protein lysates were subjected to SDS-PAGE analysis. Immunoblot analysis of the lysates was performed with anti-PARP Abs. FL indicates full length, and CF denotes cleaved fragment. (C) Isobologram analysis showing the synergistic cytotoxic effect of CDDO-Im and bortezomib in MM.1S cells. The graph (i) is derived from the values given in the table (ii). CI indicates combination index.