Table 1. Effect of afatinib on reversing ABC transporters-mediated MDR.
| Compounds | IC50 ± SD, μmol/L (Fold reversal) | |
|---|---|---|
| H460 | H460/MX20 (ABCG2) | |
| Mitoxantrone | 0.020 ± 0.004 (1.00) | 0.369 ± 0.086 (1.00) |
| +0.25 μM Afatinib | 0.009 ± 0.003 (2.14) | 0.280 ± 0.011 (1.32) |
| +0.5 μM Afatinib | 0.008 ± 0.002 (2.40)* | 0.162 ± 0.024 (2.28) |
| +1.0 μM Afatinib | 0.008 ± 0.002 (2.40)* | 0.081 ± 0.002 (4.56)** |
| +2.5 μM FTC | 0.007 ± 0.003 (2.86)** | 0.073 ± 0.015(5.05)** |
| Cisplatin | 2.815 ± 0.386 (1.00) | 7.866 ± 0.739 (1.00) |
| +1.0 μM Afatinib | 2.320 ± 0.248 (1.21) | 8.076 ± 0.804 (0.97) |
| S1 | S1-MI-80 (ABCG2) | |
| Topotecan | 0.031 ± 0.006 (1.00) | 7.599 ± 0.954 (1.00) |
| +0.25 μM Afatinib | 0.028 ± 0.004 (1.11) | 2.997 ± 0.504 (2.54)* |
| +0.5 μM Afatinib | 0.023 ± 0.006 (1.35) | 1.427 ± 0.215 (5.32)** |
| +1.0 μM Afatinib | 0.022 ± 0.005 (1.43) | 0.453 ± 0.252 (16.78)** |
| +2.5 μM FTC | 0.029 ± 0.003 (1.07) | 0.285 ± 0.070 (26.66)** |
| Cisplatin | 5.546 ± 0.144 (1.00) | 30.673 ± 0.988 (1.00) |
| +1.0 μM Afatinib | 3.575 ± 0.276 (1.55) | 30.119 ± 2.311 (0.98) |
| Mitoxantrone | 0.170 ± 0.001 (1.00) | 15.658 ± 0.981 (1.00) |
| +0.25 μM Afatinib | 0.152 ± 0.002 (1.11) | 7.318 ± 1.078 (2.14)* |
| +0.5 μM Afatinib | 0.143 ± 0.002 (1.19) | 4.964 ± 1.028 (3.15)* |
| +1.0μM Afatinib | 0.164 ± 0.001 (1.04) | 1.368 ± 0.131 (11.45)** |
| +2.5 μM FTC | 0.187 ± 0.000 (0.91) | 1.288 ± 0.013 (12.16)** |
| KB | KBv200 (ABCB1) | |
| Doxorubicin | 0.036 ± 0.007 (1.00) | 1.134 ± 0.091 (1.00) |
| + 0.025 μM Afatinib | 0.034 ± 0.003 (1.06) | 0.835 ± 0.100 (1.36) |
| +0.05 μM Afatinib | 0.032 ± 0.002 (1.13) | 0.715 ± 0.066 (1.59) |
| +0.1 μM Afatinib | 0.039 ± 0.002 (0.92) | 0.614 ± 0.027 (1.84) |
| +10 μM Verapamil | 0.030 ± 0.005 (1.20) | 0.120 ± 0.031 (9.45)** |
| Paclitaxel | 0.002 ± 0.003 (1.00) | 0.348 ± 0.192 (1.00) |
| +0.025 μM Afatinib | 0.019 ± 0.003 (1.05) | 0.401 ± 0.012 (0.87) |
| +0.05 μM Afatinib | 0.018 ± 0.004 (1.11) | 0.302 ± 0.230 (1.15) |
| +0.1 μM Afatinib | 0.015 ± 0.002 (1.33) | 0.138 ± 0.023 (2.52) |
| +10 μM Verapamil | 0.019 ± 0.005 (1.05) | 0.051 ± 0.342 (6.82)** |
| Cisplatin | 0.527 ± 0.998 (1.00) | 0.901 ± 1.233 (1.00) |
| +0.1 μM Afatinib | 0.589 ± 2.112 (0.89) | 1.021 ± 0.772 (0.88) |
| MCF-7 | MCF-7/ADR(ABCB1) | |
| Doxorubicin | 0.449 ± 0.114 (1.00) | 15.963 ± 1.014 (1.00) |
| +0.025 μM Afatinib | 0.298 ± 0.184 (1.51) | 10.966 ± 0.222 (1.46) |
| +0.05 μM Afatinib | 0.368 ± 0.119 (1.22) | 10.156 ± 0.612 (1.57) |
| +0.1 μM Afatinib | 0.361 ± 0.118 (1.24) | 8.462 ± 0.164 (1.88) |
| +10 μM Verapamil | 0.401 ± 0.096 (1.12) | 1.414 ± 0.078 (11.3)** |
| Cisplatin | 5.011 ± 0.183 (1.00) | 5.56 ± 1.234 (1.00) |
| +0.1μM Afatinib | 5.883 ± 2.012 (0.84) | 5.012 ± 2.061 (1.09) |
| HL60 | HL60/ADR(ABCC1) | |
| Doxorubicin | 0.028 ± 0.003 (1.00) | 6.227 ± 0.588 (1.00) |
| +0.025 μM Afatinib | 0.027 ± 0.001 (1.04) | 4.795 ± 0.305 (1.30) |
| +0.05 μM Afatinib | 0.034 ± 0.002 (0.82) | 5.155 ± 0.543 (1.21) |
| +0.1 μM Afatinib | 0.026 ± 0.001 (1.08) | 5.521 ± 0.466 (1.13) |
| +0.7 μM MK571 | 0.024 ± 0.003 (0.86) | 2.007 ± 0.023 (3.10)* |
| Cisplatin | 1.533 ± 0.143 (1.00) | 1.587 ± 1.234 (1.00) |
| +0.1 μM Afatinib | 1.626 ± 0.917 (0.95) | 1.603 ± 0.102 (0.99) |
Cell survival was determined by MTT assay as described in Materials and Methods. The fold reversal of MDR (values given in parentheses) was calculated by dividing the IC50 for cells with anticancer drugs in the absence of afatinib by that obtained in the presence of afatinib. Data represent Mean ± SD of at least three independent experiments. *p < 0.05, **p < 0.01.