Table 1. Effect of PPD derivatives on reversing ABCB1-mediated drug resistance of KB cells.
| Compounds | IC50 ± SD (μM)a (fold reversalb) | |||
|---|---|---|---|---|
| KB | KB/VCR(ABCB1) | |||
| Adriamycin | 0.972 ± 0.273 | (1.00) | 6.245 ± 1.192 | (1.00) |
| + 1.25 μM PPD12 | 0.917 ± 0.054 | (1.06) | 1.469 ± 0.032 | (4.25)* |
| + 2.5 μM PPD12 | 0.876 ± 0.063 | (1.11) | 1.174 ± 0.025 | (5.32)* |
| + 5 μM PPD12 | 0.667 ± 0.075 | (1.46) | 0.483 ± 0.196 | (12.92)** |
| + 10 μM Verapamil | 0.565 ± 0.016 | (1.72) | 0.474 ± 0.164 | (13.17)** |
| Paclitaxel | 0.073 ± 0.004 | (1.00) | 5.174 ± 0.421 | (1.00) |
| + 1.25 μM PPD12 | 0.054 ± 0.004 | (1.33) | 1.487 ± 0.097 | (3.48)* |
| + 2.5 μM PPD12 | 0.051 ± 0.006 | (1.42) | 1.080 ± 0.083 | (4.79)* |
| + 5 μM PPD12 | 0.050 ± 0.003 | (1.36) | 0.729 ± 0.011 | (7.10)* |
| + 10 μM Verapamil | 0.038 ± 0.005 | (1.92) | 0.319 ± 0.029 | (16.22)** |
| Cisplatin | 2.755 ± 0.314 | (1.00) | 3.637 ± 0.325 | (1.00) |
| + 1.25 μM PPD12 | 1.583 ± 0.054 | (1.74) | 2.186 ± 0.504 | (1.66) |
| + 2.5 μM PPD12 | 1.524 ± 0.264 | (1.81) | 2.043 ± 0.273 | (1.78) |
| + 5 μM PPD12 | 1.458 ± 0.297 | (1.89) | 2.865 ± 0.956 | (1.27) |
| + 10 μM Verapamil | 1.951 ± 0.504 | (1.41) | 3.075 ± 4.884 | (1.18) |
| Adriamycin | 0.557 ± 0.061 | (1.00) | 6.775 ± 0.511 | (1.00) |
| + 1.25 μM PPD11 | 0.583 ± 0.054 | (0.96) | 2.547 ± 0.504 | (2.66)* |
| + 2.5 μM PPD11 | 0.524 ± 0.064 | (1.06) | 2.437 ± 0.273 | (2.78)* |
| + 5 μM PPD11 | 0.458 ± 0.097 | (1.22) | 2.072 ± 0.956 | (3.27)* |
| + 10 μM Verapamil | 0.451 ± 0.054 | (1.24) | 0.446 ± 0.084 | (15.18)** |
| Paclitaxel | 0.044 ± 0.003 | (1.00) | 3.217 ± 0.526 | (1.00) |
| + 1.25 μM PPD11 | 0.048 ± 0.002 | (0.91) | 1.828 ± 0.443 | (1.76) |
| + 2.5 μM PPD11 | 0.042 ± 0.004 | (1.04) | 1.496 ± 0.572 | (2.15)* |
| + 5 μM PPD11 | 0.047 ± 0.006 | (0.93) | 1.041 ± 0.378 | (3.09)* |
| + 10 μM Verapamil | 0.035 ± 0.005 | (1.27) | 0.218 ± 0.095 | (14.73)** |
| Cisplatin | 2.237 ± 0.923 | (1.00) | 5.596 ± 1.403 | (1.00) |
| + 1.25 μM PPD11 | 2.306 ± 0.721 | (0.97) | 4.441 ± 0.923 | (1.26) |
| + 2.5 μM PPD11 | 1.896 ± 0.567 | (1.18) | 4.085 ± 1.104 | (1.37) |
| + 5 μM PPD11 | 2.513 ± 0.778 | (0.89) | 4.909 ± 1.034 | (1.14) |
| + 10 μM Verapamil | 1.849 ± 0.729 | (1.21) | 4.477 ± 0.921 | (1.25) |
| Adriamycin | 0.717 ± 0.055 | (1.00) | 5.345 ± 1.074 | (1.00) |
| + 1.25 μM PPD | 0.739 ± 0.014 | (0.97) | 4.143 ± 0.946 | (1.29) |
| + 2.5 μM PPD | 0.763 ± 0.075 | (0.94) | 2.582 ± 0.547 | (2.07)* |
| + 5 μM PPD | 0.710 ± 0.034 | (1.01) | 2.419 ± 0.826 | (2.21)* |
| + 10 μM Verapamil | 0.771 ± 0.054 | (0.93) | 0.386 ± 0.076 | (13.83)** |
| Paclitaxel | 0.057 ± 0.004 | (1.00) | 4.118 ± 0.725 | (1.00) |
| + 1.25 μMPPD | 0.049 ± 0.002 | (1.17) | 3.778 ± 0.847 | (1.09) |
| + 2.5 μM PPD | 0.054 ± 0.004 | (1.06) | 1.898 ± 0.252 | (2.17)* |
| + 5 μM PPD | 0.063 ± 0.003 | (0.91) | 1.481 ± 0.637 | (2.78)* |
| + 10 μM Verapamil | 0.041 ± 0.002 | (1.39) | 0.246 ± 0.048 | (16.71)** |
| Cisplatin | 2.384 ± 0.217 | (1.00) | 3.631 ± 0.458 | (1.00) |
| + 1.25 μMPPD | 2.563 ± 0.154 | (0.93) | 3.425 ± 0.924 | (1.06) |
| + 2.5 μM PPD | 2.458 ± 0.436 | (0.97) | 3.077 ± 0.617 | (1.18) |
| + 5 μM PPD | 2.110 ± 0.927 | (1.13) | 3.782 ± 0.762 | (0.96) |
| + 10 μM Verapamil | 2.148 ± 0.411 | (1.11) | 2.859 ± 0.719 | (1.27) |
a
IC50 values are represented as mean ± SD of three independent experiments performed in triplicate.
b
The fold-reversal of MDR (values given in parenthesis) was calculated by dividing the IC50 for cells with the anticancer drugs in the absence of inhibitor by that obtained in the presence of inhibitor. Cell survival was performed by MTT assay as described in “Materials and Methods”. Verapamil, MK571 and FTC were used as a positive control of ABCB1, ABCC1 and ABCG2 inhibitor, respectively.
*
p < 0.05, significantly different from those obtained in the absence of inhibitor.
**
p < 0.01, significantly different from those obtained in the absence of inhibitor.