Table 1.
Effect of FG020326 on reversing ABCB1-, ABCC1-, ABCC4-, ABCG2-, and LRP-mediated drug resistance mediated drug resistance
| IC50 ± SD (µM) (fold-reversal) | ||||
|---|---|---|---|---|
| MCF-7 | MCF-7/adr (ABCB1) | |||
| Doxorubicin (µM) | 0.081±0.010 | (1.0) | 14.263±1.423 | (1.0) |
| +1.25 µM FG020326 | 0.085±0.014 | (1.0) | 2.219±0.222** | (6.4) |
| +2.5 µM FG020326 | 0.080±0.017 | (1.0) | 1.481±0.117** | (9.6) |
| +5 µM FG020326 | 0.089±0.021 | (0.9) | 0.996±0.134** | (14.3) |
| Vincristine (µM) | 0.059±0.009 | (1.0) | 4.017±0.656 | (1.0) |
| +1.25 µM FG020326 | 0.063±0.012 | (0.9) | 1.715±0.165** | (2.3) |
| +2.5 µM FG020326 | 0.057±0.014 | (1.0) | 0.874±0.287** | (4.6) |
| +5 µM FG020326 | 0.065±0.016 | (0.9) | 0.375±0.089** | (10.7) |
| Paclitaxel (nM) | 6.905±0.903 | (1.0) | 339.772±38.655 | (1.0) |
| +1.25 µM FG020326 | 5.847±1.212 | (1.1) | 98.274±16.325** | (3.5) |
| +2.5 µM FG020326 | 7.093±0.881 | (1.0) | 38.503±7.623** | (8.8) |
| +5 µM FG020326 | 7.133±0.651 | (1.0) | 15.453±3.588** | (22.0) |
| Cisplatin (µM) | 3.553±0.213 | (1.0) | 2.650±0.252 | (1.0) |
| +5 µM FG020326 | 3.250±0.305 | (0.9) | 2.941±0.325 | (0.9) |
| KB | KBv200 (ABCB1) | |||
| Doxorubicin (µM) | 0.020±0.010 | (1.0) | 0.979±0.123 | (1.0) |
| +1.25 µM FG020326 | 0.019±0.012 | (1.0) | 0.234±0.028** | (4.2) |
| +2.5 µM FG020326 | 0.020±0.018 | (1.0) | 0.123±0.018** | (8.0) |
| +5 µM FG020326 | 0.022±0.020 | (0.9) | 0.080±0.024** | (12.2) |
| Vincristine (µM) | 0.028±0.009 | (1.0) | 1.318±0.256 | (1.0) |
| +1.25 µM FG020326 | 0.023±0.013 | (1.0) | 0.079±0.025** | (16.7) |
| +2.5 µM FG020326 | 0.024±0.012 | (1.0) | 0.038±0.011** | (34.7) |
| +5 µM FG020326 | 0.024±0.010 | (1.0) | 0.023±0.005** | (57.3) |
| Paclitaxel (nM) | 1.383±0.148 | (1.0) | 48.342±4.119 | (1.0) |
| +1.25 µM FG020326 | 1.333±0.162 | (1.0) | 9.583±1.039** | (5.0) |
| +2.5 µM FG020326 | 1.306±0.225 | (1.0) | 4.696±0.415** | (10.3) |
| +5 µM FG020326 | 1.387±0.130 | (1.1) | 1.590±0.116** | (30.4) |
| 5-FU (µM) | 3.561±0.379 | (1.0) | 3.122±0.324 | (1.0) |
| +5 µM FG020326 | 3.431±0.358 | (1.0) | 3.302±0.210 | (0.7) |
| KB-3-1 | KB-CV60 (ABCC1) | |||
| Vincristine (µM) | 7.261±0.724 | (1.0) | 88.562±8.279 | (1.0) |
| +5 µM FG020326 | 8.029±0.810 | (0.9) | 95.429±9.351 | (0.9) |
| NIH3T3 | NIH3T3/MRP-4-2 (ABCC4) | |||
| Vincristine (µM) | 0.324±0.024 | (1.0) | 7.247±0.779 | (1.0) |
| +5 µM FG020326 | 0.378±0.056 | (0.9) | 8.259±1.951 | (0.9) |
| S1 | S1-M1-80 (ABCG2) | |||
| Topotecan (µM) | 0.084±0.024 | (1.0) | 12.031±1.279 | (1.0) |
| +5 µM FG020326 | 0.192078±0.010 | (1.1) | 11.407±1.351 | (1.0) |
| SW1573 | SW1573/2R120 (LRP) | |||
| Doxorubicin (µM) | 0.116±0.024 | (1.0) | 1.545±0.279 | (1.0) |
| +5 µM FG020326 | 0.089±0.020 | (1.2) | 1.536±0.351 | (1.0) |
Cell survival was determined by MTT assay as described in “Materials and Methods”. 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 for cells with the anticancer drug in the absence of FG020326 by that obtained in the presence of FG020326.
**
represents P<0.01 for the values versus that obtained in the absence of FG020326.