Table 2.
Compounds | EC50 | ||||||
---|---|---|---|---|---|---|---|
Mock | WT | M184K | N297S | K304N | P403L | E757K | |
ATRA (μM) | 40.0 ± 10.1 | 42.1 ± 4.8 | 43.4 ± 3.2 | 48.1 ± 8.0 | 40.3 ± 4.8 | 41.0 ± 2.9 | 42.0 ± 4.3 |
Azathioprine (μM) | 4.2 ± 1.0 | 21.5 ± 1.0 * | 14.3 ± 1.8 *,** | 12.6 ± 2.4 *,** | 12.6 ± 2.2 *,** | 17.9 ± 1.0 * | 15.2 ± 3.3 *,** |
Etoposide (nM) | 204.9 ± 16.2 | 256.6 ± 31.7 | 210.3 ± 13.2 | 254.1 ± 28.2 | 326.3 ± 33.6 * | 321.0 ± 14.6 * | 208.4 ± 17.9 |
5-FU (μM) | 7.7 ± 1.4 | 6.3 ± 2.2 | 11.1 ± 1.4 | 4.5 ± 1.2 | 11.0 ± 2.7 | 4.3 ± 1.0 | 5.9 ± 1.2 |
6-Mercaptopurine (μM) | 1.9 ± 0.4 | 9.1 ± 1.8 * | 6.4 ± 0.7 * | 6.6 ± 0.9 * | 4.6 ± 0.3 ** | 6.4 ± 0.5 * | 5.1 ± 1.4 ** |
SN-38 (nM) | 8.7 ± 1.1 | 45.5 ± 10.2 * | 50.2 ± 6.6 * | 29.5 ± 8.5 * | 22.5 ± 0.3 ** | 24.4 ± 7.4 ** | 21.6 ± 1.6 ** |
Vincristine (nM) | 2.9 ± 1.1 | 1.6 ± 0.5 | 2.1 ± 0.7 | 2.1 ± 0.8 | 2.3 ± 0.4 | 1.9 ± 0.4 | 1.7 ± 0.3 |
Definitions: ATRA, All-trans-retinoic acid; 5-FU, 5-Fluorouracil; SN-38, 7-Ethyl-10-hydroxy-camptothecin. The drug resistance properties of cells established using the Flp-In™ system were evaluated, as described in Materials and Methods. Data are expressed as mean values ± S.D. (n = 3–6). Statistical analyses for significance were performed using One-way ANOVA and Tukey HSD test (* p < 0.01 compared to the Mock group; ** p < 0.01 compared with the wild type (WT)).