Table 1.
Chemosensitization effect of midostaurin on drug resistance mediated by ABCB1, ABCC1 or ABCG2 in HEK293 cells.
| Treatment | Concentration (nM) | Mean IC50a ± SD and (FRb) |
|
|---|---|---|---|
| pcDNA-HEK293 [nM] | MDR19-HEK293 (ABCB1) [nM] | ||
| Paclitaxel | – | 1.67 ± 0.18 (1.0) | 813.43 ± 100.82 (1.0) |
| + midostaurin | 20 | 1.47 ± 0.15 (1.1) | 295.11 ± 41.97** (2.8) |
| + midostaurin | 50 | 1.34 ± 0.14 (1.2) | 118.47 ± 16.94*** (6.9) |
| + verapamil | 5000 | 1.29 ± 0.15 (1.3) | 6.85 ± 1.20*** (118.7) |
| pcDNA-HEK293 [nM] | MRP1-HEK293 (ABCC1) [μM] | ||
| Etoposide | – | 282.62 ± 52.41 (1.0) | 77.95 ± 12.67 (1.0) |
| + midostaurin | 20 | 234.00 ± 40.53 (1.2) | 80.21 ± 16.67 (1.0) |
| + midostaurin | 50 | 237.94 ± 41.26 (1.2) | 70.31 ± 12.09 (1.1) |
| + MK-571 | 25000 | 172.78 ± 35.09* (1.6) | 14.17 ± 1.47*** (5.5) |
| pcDNA-HEK293 [nM] | R482-HEK293 (ABCG2) [nM] | ||
| SN-38 | – | 4.61 ± 0.89 (1.0) | 125.14 ± 19.03 (1.0) |
| + midostaurin | 20 | 5.17 ± 0.93 (0.9) | 134.28 ± 18.11 (0.9) |
| + midostaurin | 50 | 4.87 ± 0.98 (0.9) | 133.55 ± 19.81 (0.9) |
| + Ko143 | 1000 | 4.60 ± 0.92 (1.0) | 2.74 ± 0.66*** (45.7) |
Abbreviation: FR, fold-reversal.
*
P < 0.05
**
P < 0.01
***
P < 0.001.
a
IC50 values are mean ± SD calculated from dose-response curves obtained from at least three independent experiments using cytotoxicity assay as described in Materials and methods.
b
FR values were calculated by dividing IC50 values of cells treated with drug substrate in the absence of midostaurin or a reference inhibitor verapamil, MK-571 or Ko143 by IC50 values of cells treated with the same drug in the presence of midostaurin or a reference inhibitor.