Figure 3.
Degrasyn interacts with bortezomib to synergize growth inhibition in MCL cells. (A) Typical MCL (Mino) and BV-MCL (Z-138) cells were treated with a combination of bortezomib and degrasyn in a dose-dependent manner as indicated and analyzed for cell proliferation using thymidine incorporation assays. A significant cell growth inhibition was observed in degrasyn plus bortezomib treatment compared to single agent alone in both cell lines, Mino (degrasyn alone vs. BZ (15 nM); p=0.015) and Z-138 (degrasyn alone vs. BZ (12.5 nM); p=0.0018). The data shown are the means and ranges of triplicate cultures of three independent experiments. Error bars represent standard deviation. Statistical analysis was determined using the student t-test. (B) Typical MCL (Mino) and BV-MCL (Z-138) cells were left untreated or treated with low dose of degrasyn (DG, 1 uM), bortezomib (BZ, 10 nM), or the combination of both. Cell number was determined by tryphan blue exclusion. The data shown are the means and ranges of triplicate cultures of two independent experiments. Error bars represent standard deviation. (C) The drug combination index for bortezomib and degrasyn (CI) was calculated by using the CalcuSyn software program. A combination index value of 1 indicated an additive effect of the two drugs. Combination index values less than 1 indicated synergy; the lower the value, the stronger the synergy. In contrast, combination index values greater than 1 indicated antagonism. (D) Representative normalized isobolograms demonstrating the synergy between bortezomib and degrasyn in typical MCL and BV-MCL cells.