Table 1.
Effect of TMP195 on drug resistance mediated by major ATP-binding cassette (ABC) drug efflux transporters in HEK293 cells transfected with ABCB1, ABCC1 or ABCG2.
| Treatment | Concentration (μM) | Mean IC50 † ± SD and (FR ‡) | |
|---|---|---|---|
| pcDNA-HEK293 (Parental) (nM) | MDR19-HEK293 (Resistant) (nM) | ||
| Paclitaxel | - | 2.45 ± 0.47 (1.0) | 1020.80 ± 176.45 (1.0) |
| +TMP195 | 1 | 2.01 ± 0.24 (1.2) | 462.33 ± 84.71 ** (2.2) |
| +TMP195 | 2 | 1.87 ± 0.32 (1.3) | 222.28 ± 26.22 ** (4.6) |
| +TMP195 | 3 | 2.19 ± 0.38 (1.1) | 160.98 ± 35.26 ** (6.3) |
| +TMP195 | 5 | 1.91 ± 0.27 (1.3) | 62.69 ± 6.33 *** (16.3) |
| +Verapamil | 5 | 1.81 ± 0.41 (1.4) | 10.03 ± 1.53 *** (101.8) |
| pcDNA-HEK293 (parental) (nM) | R482-HEK293 (resistant) (nM) | ||
| Mitoxantrone | - | 2.24 ± 0.38 (1.0) | 65.08 ± 6.00 (1.0) |
| +TMP195 | 1 | 1.87 ± 0.34 (1.2) | 20.53 ± 4.07 *** (3.2) |
| +TMP195 | 2 | 1.71 ± 0.36 (1.3) | 11.86 ± 1.61 *** (5.5) |
| +TMP195 | 3 | 1.62 ± 0.24 (1.4) | 12.42 ± 2.33 *** (5.3) |
| +TMP195 | 5 | 1.56 ± 0.29 (1.4) | 6.70 ± 1.33 *** (9.7) |
| +Ko143 | 3 | 1.81 ± 0.32 (1.2) | 3.60 ± 0.38 *** (18.1) |
| pcDNA-HEK293 (parental) (nM) | MRP1-HEK293 (resistant) (μM) | ||
| Etoposide | - | 175.37 ± 35.99 (1.0) | 86.22 ± 11.07 (1.0) |
| +TMP195 | 1 | 185.10 ± 30.36 (0.9) | 110.60 ± 18.86 (0.8) |
| +TMP195 | 2 | 236.17 ± 52.11 (0.7) | 104.62 ± 16.93 (0.8) |
| +TMP195 | 3 | 258.68 ± 38.05 (0.7) | 96.09 ± 29.32 (0.9) |
| +TMP195 | 5 | 172.29 ± 30.28 (1.0) | 72.24 ± 9.20 (1.2) |
| +MK-571 | 25 | 160.23 ± 27.21 (1.1) | 19.20 ± 1.47 *** (4.5) |
Abbreviation: FR, fold-reversal. † IC50 values are mean ± SD calculated from dose-response curves obtained from at least three independent experiments using cytotoxicity assay as described in Section 4. ‡ FR values were calculated by dividing IC50 values of cells treated with a particular therapeutic drug in the absence of TMP195 or a respective reference inhibitor by IC50 values of cells treated with the same therapeutic drug in the presence of TMP195 or a respective reference inhibitor. * p < 0.05; ** p < 0.01; *** p < 0.001.