Table 2.
VS-4718 sensitized ABCB1-gene-transfected cells to ABCB1 substrates.
| Treatment | IC50 ±SDa (RFb) | |
|---|---|---|
| HEK293/pcDNA3.1 (μM) | HEK293/ABCB1 (μM) | |
| Doxorubicin | 0.065 ± 0.008 (1.00) | 1.375 ± 0.079 (21.15) |
| +VS-4718 (1 μM) | 0.066 ± 0.009 (1.01) | 0.491 ± 0.049 (7.55)* |
| +VS-4718 (3 μM) | 0.055 ± 0.013 (0.84) | 0.220 ± 0.034 (3.39)* |
| +Verapamil (3 μM) | 0.064 ± 0.007 (0.99) | 0.121 ± 0.017 (1.85)* |
| Paclitaxel | 0.043 ± 0.001 (1.00) | 1.054 ± 0.200 (24.80) |
| +VS-4718 (1 μM) | 0.047 ± 0.004 (1.11) | 0.498 ± 0.062 (11.73)* |
| +VS-4718 (3 μM) | 0.037 ± 0.005 (0.86) | 0.313 ± 0.053 (7.37)* |
| +Verapamil (3 μM) | 0.032 ± 0.009 (0.74) | 0.297 ± 0.055 (6.99)* |
| Cisplatin | 1.071 ± 0.144 (1.00) | 1.259 ± 0.425 (1.18) |
| +VS-4718 (1 μM) | 1.186 ± 0.443 (1.11) | 1.260 ± 0.563 (1.18) |
| +VS-4718 (3 μM) | 1.105 ± 0.371 (1.03) | 1.272 ± 0.217 (1.19) |
| +Verapamil (3 μM) | 0.971 ± 0.206 (0.91) | 1.293 ± 0.368 (1.21) |
a
IC50 values were determined by MTT assay as described in “Materials and Methods,” and were obtained from three independent experiments in triplicate.
b
Resistance fold (RF) was calculated from dividing the IC50 values of resistance cells (HEK293/ABCB1) by the IC50 of parental cells (HEK293/pcDNA3.1) in the presence or absence of VS-4718 or positive control inhibitor.
*
indicates p < 0.05 vs. group treated with antineoplastic drug only.