Effect of MDR drug efflux transporter expression on growth inhibitory effect of bortezomib and expoxyketone-based proteasome inhibitors
Data presented are the mean of three to six separate experiments ± S.D. Values in parentheses depict the resistance factor [ratio of IC50 values of selected cell line over parental (WT) cell line].
| Cell Line | MDR Phenotype | Reference | Bortezomib IC50 | Carfilzomib IC50 | ONX 0912 IC50 | ONX 0914 IC50 |
|---|---|---|---|---|---|---|
| nM | ||||||
| CEM/WT | None | 1.6 ± 0.7 (1) | 0.84 ± 0.20 (1) | 14.8 ± 1.1 (1) | 46.6 ± 7.9 (1) | |
| 2008/WT | None | 9.2 ± 1.6 (1) | 10.6 ± 6.2 (1) | 40.0 ± 6.9 (1) | 377 ± 206 (1) | |
| HEK293/WT | None | 5.1 ± 1.8 (1) | 24.9 ± 5.5 (1) | 38.3 ± 6.7 (1) | 330 ± 26 (1) | |
| MCF7/WT | None | 6.2 ± 1.3 (1) | 5.2 ± 2.2 (1) | 37 ± 10 (1) | 156 ± 15 (1) | |
| CEM/VLB | Pgp/MDR1 (+++) | Zamora et al 1988 | 7.2 ± 1.9 (4.5) | 102 ± 35 (114) | 366 ± 43 (23) | 6790 ± 1310 (162) |
| CEM/CHQ | MRP1 (+) | Oerlemans et al., 2006 | 3.3 ± 0.4 (2.1) | 1.9 ± 0.3 (2.3) | 27.0 ± 2.0 (1.9) | 83 ± 11 (1.9) |
| 2008/MRP1 | MRP1 (+++) | Scheffer et al., 2000 | 8.3 ± 3.7 (0.9) | 12.3 ± 4.5 (1.3) | 45.7 ± 11.6 (1.1) | 372 ± 70 (1.1) |
| 2008/MRP2 | MRP2 (+++) | Scheffer et al.,2000 | 8.5 ± 3.5 (0.9) | 10.8 ± 5.9 (1.0) | 45.0 ± 7.9 (1.1) | 290 ± 47 (0.9) |
| 2008/MRP3 | MRP3 (+++) | Scheffer et al., 2000 | 7.6 ± 2.9 (0.8) | 9.9 ± 4.2 (1.0) | 40.3 ± 3.1 (1.0) | 320 ± 44 (1.1) |
| HEK293/MRP4 | MRP4 (+++) | Wielinga et al., 2002 | 5.1 ± 1.7 (1.0) | 34.3 ± 9.7 (1.3) | 38.3 ± 5.0 (1.0) | 321 ± 69 (1.0) |
| HEK293/MRP5 | MRP5 (+++) | Wielinga et al., 2002 | 3.1 ± 1.4 (0.7) | 14.1 ± 4.3 (0.7) | 19.5 ± 2.1 (0.6) | 211 ± 75 (0.7) |
| CEM/SSZ | BCRP (+) | van der Heijden et al., 2004 | 1.7 ± 0.2 (1.1) | 0.69 ± 0.14 (0.9) | 8.0 ± 1.1 (0.6) | 49.0 ± 7.6 (1.1) |
| MCF7/MR | BCRP (+++) | Taylor 1991 | 2.3 ± 1.0 (0.4) | 1.5 ± 0.8 (0.3) | 8.9 ± 2.5 (0.3) | 60 ± 19 (0.4) |