Figure 5.

Combination treatment with MTI-101 and bortezomib augments survival in vitro and in vivo. (A) 5TGM1 cells were treated with varying concentrations of MTI-101, bortezomib or the combination of both drugs for 72 hours using a bone marrow stroma model as described in materials and methods. Combination indexes (CI) for duplicate wells were calculated at 30 and 72 hrs. (B) 1 × 10⁶ 5TGM1 MM cells were injected into 6–8 week old C57BL/KaLwRijHsd mice via tail vein. At day 10, mice were treated with 10 mg/kg of MTI-101 and/or 0.5 mg/kg bortezomib three times a week for three weeks (10 mice per group). Mice were monitored daily for survival. Mean survival times for vehicle control, bortezomib only (p < 0.02, log-rank sum), MTI-101 only (p < 0.01, log rank sum), and MTI-101/bortezomib (p < 0.001, log rank sum) combination therapy were 36, 42, 45.5, and 72.5 days, respectively. (C) IgG2B serum levels were measured by ELISA once a week for 4 weeks to determine myeloma levels in the peripheral blood. At day 28 all drug treatment groups showed a significant decrease in IgG2B levels compared to control animals (p < 0.05).