Table 1.
Effect of crizotinib on reversing ABCB1-, ABCC1- and ABCG2-mediated MDR in pairs of sensitive and drug-resistant cell lines
| IC50± SD (µM) (fold-reversal) | ||||
|---|---|---|---|---|
| Compounds | MCF-7 | MCF-7/adr (ABCB1) | ||
| Doxorubicin | 0.341 ± 0.029 | (1.00) | 8.321 ± 0.602 | (1.00) |
| +0.375 µM Crizotinib | 0.339 ± 0.041 | (1.01) | 2.119 ± 0.151** | (4.13) |
| +0.75 µM Crizotinib | 0.326 ± 0.017 | (1.01) | 1.038 ± 0.062** | (8.50) |
| +1.5 µM Crizotinib | 0.303 ± 0.016 | (1.13) | 0.849 ± 0.051** | (10.2) |
| +10 µM Verapamil | 0.334 ± 0.020 | (1.02) | 0.496 ± 0.005** | (17.8) |
| Paclitaxel | 0.031 ± 0.025 | (1.00) | 0.877 ± 0.021 | (1.00) |
| +0.375 µM Crizotinib | 0.030 ± 0.014 | (1.03) | 0.381 ± 0.019** | (2.32) |
| +0.75 µM Crizotinib | 0.029 ± 0.028 | (1.07) | 0.303 ± 0.021** | (2.68) |
| +1.5 µM Crizotinib | 0.030 ± 0.098 | (1.03) | 0.217 ± 0.025** | (4.00) |
| +10 µM Verapamil | 0.027 ± 0.019 | (1.14) | 0.052 ± 0.065** | (16.9) |
| Cisplatin | 15.431 ± 1.571 | (1.00) | 18.672 ± 0.671 | (1.00) |
| +1.5 µM Crizotinib | 16.012 ± 0.468 | (1.18) | 17.956 ± 0.997 | (1.04) |
| +10 µM Verapamil | 15.285 ± 0.299 | (1.26) | 18.316 ± 0.346 | (1.02) |
| KB | KBv200 (ABCB1) | |||
| Doxorubicin | 0.190 ± 0.061 | (1.00) | 6.536 ± 0.219 | (1.00) |
| +0.375 µM Crizotinib | 0.205 ± 0.074 | (0.93) | 4.136 ± 0.137* | (1.58) |
| +0.75 µM Crizotinib | 0.181 ± 0.031 | (1.04) | 2.422 ± 0.149** | (2.70) |
| +1.5 µM Crizotinib | 0.169 ± 0.006 | (1.12) | 1.578 ± 0.341** | (4.14) |
| +10 µM Verapamil | 0.158 ± 0.053 | (1.20) | 0.408 ± 0.083** | (16.0) |
| Paclitaxel | 0.0010 ± 0.0012 | (1.00) | 0.388 ± 0.023 | (1.00) |
| +0.375 µM Crizotinib | 0.0011 ± 0.0007 | (0.90) | 0.201 ± 0.003** | (1.93) |
| +0.75 µM Crizotinib | 0.0010 ± 0.0006 | (1.00) | 0.145 ± 0.042** | (2.67) |
| +1.5 µM Crizotinib | 0.0009 ± 0.0003 | (1.11) | 0.105 ± 0.049** | (3.70) |
| +10 µM Verapamil | 0.0009 ± 0.0004 | (1.11) | 0.017 ± 0.002** | (22.8) |
| Cisplatin | 2.284 ± 0.219 | (1.00) | 3.631 ± 0.058 | (1.00) |
| +1.5 µM Crizotinib | 2.503 ± 0.061 | (0.91) | 3.393 ± 0.764 | (1.07) |
| +10 µM Verapamil | 2.461 ± 0.021 | (0.93) | 2.980 ± 0.023 | (1.22) |
| HL60 | HL60/adr (ABCC1) | |||
| Doxorubicin | 0.033 ± 0.002 | (1.00) | 5.950 ± 0.259 | (1.00) |
| +0.375 µM Crizotinib | 0.032 ± 0.002 | (1.03) | 4.605 ± 0.389 | (0.99) |
| +0.75 µM Crizotinib | 0.029 ± 0.004 | (1.14) | 4.656 ± 0.211 | (1.31) |
| +1.5 µM Crizotinib | 0.030 ± 0.002 | (1.10) | 4.889 ± 0.362 | (1.21) |
| +50 µM MK571 | 0.031 ± 0.002 | (1.06) | 0.801 ± 0.401** | (7.89) |
| S1 | S1-M1-80 (ABCG2) | |||
| Topotecan | 0.517 ± 0.017 | (1.00) | 18.671 ± 0.164 | (1.00) |
| +0.25 µM Crizotinib | 0.515 ± 0.022 | (1.00) | 17.515 ± 0.158 | (1.06) |
| +0.5 µM Crizotinib | 0.514 ± 0.024 | (1.01) | 17.839 ± 0.259 | (1.04) |
| +1.0 µM Crizotinib | 0.485 ± 0.065 | (1.08) | 14.746 ± 0.808 | (1.14) |
| +2.5 µM FTC | 0.499 ± 0.088 | (1.06) | 2.051 ± 0.032** | (9.13) |
Cell survival was determined by MTT. Data are the means ± SD of at least three independent experiments performed in triplicate. The fold reversal of MDR was calculated by dividing the IC50 value for cells with the anticancer drug in the absence of inhibitor by that obtained in the presence of inhibitor.
*
P < 0.05,
**
P < 0.01, significantly different from those obtained in the absence of inhibitor.