Table 1. Summary of interactions between IBP inhibitors and 17-AAG in myeloma cells.
| IBP inhibitor |
Cell line |
||||||
|---|---|---|---|---|---|---|---|
| RPMI-8226 | U266 | MM.1S | H929 | ALMC-2 | MC/CAR | RL | |
| Concurrent with 17-AAG | |||||||
| Lov | Syn (0.56) | Add (1.00) | Add (0.95) | Ant (1.32) | Add (0.88) | Add (0.84) | Add (1.12) |
| 3-PEHPC | Syn (0.66) | Add (0.87) | Add (0.93) | Syn (0.75) | Insensitivea | Ant (1.5) | Ant (1.29) |
| Pre-treatment | |||||||
| Lov | Syn (0.31) | Syn (0.58) | Add (1.19) | Add (0.91) | Add (0.83) | Add (1.17) | Add (1.09) |
| 3-PEHPC | Syn (0.67) | Syn (0.67) | Add (0.95) | Add (0.82) | Insensitive | Ant (1.59) | Ant (1.85) |
Cells were incubated in the presence of an IBP inhibitor (1–25 μM lovastatin (Lov) or 0.2–5 mM 3-PEHPC) and/or 17-AAG (0.1–2.5 μM) for either 48 h concurrently or 24 h pre-treatment with IBP inhibitor followed by a 24-h concurrent treatment with 17-AAG. MTT cytotoxicity assays were performed. Isobologram analysis was used to determine the combination indices (CI) for each drug combination for ED30 (CI shown in parenthesis). An interaction was determined to be synergistic (Syn) if the CI was <0.8, antagonistic (Ant) if the CI was >1.2 and additive (Add) for CI between 0.8 and 1.2. The CIs are representative of 2–3 independent experiments.
At tested concentrations, 3-PEHPC induced less than a 10% decrease in MTT activity in ALMC-2 cells, and therefore isobologram analysis was not performed.