Drug resistance profiles of ABCG2 WT and variants
The drug resistance profiles of ABCG2 WT and variants were obtained by incubating Flp-In-293/ABCG2 WT, F431L, S441N, or F489L cells in the presence of SN-38, mitoxantrone, doxorubicin, or daunorubicin at different concentrations (0–100 μM) as described under Materials and Methods. IC50 values were calculated from dose-response curves (i.e., cell survival versus drug concentration). Drug resistance ratio = (IC50 value for cells expressing ABCG2 WT or variant)/(IC50 value for mock cells). Data are expressed as mean values ± S.D. (n = 3). Statistical analyses were performed by using Microsoft Excel 2003 software (Microsoft, Redmond, WA). The statistical significance was determined according to the two-sided Student's t test.
| Anticancer Drug | IC50 and Drug Resistance Ratio | ||||
|---|---|---|---|---|---|
| Mock | WT | F431L | S441N | F489L | |
| nM (-fold) | |||||
| SN-38 | 0.9 ± 0.1 (1.0) | 42.1 ± 3.1 (46.8)* | 11.5 ± 0.9 (12.7)* | 0.7 ± 0.1 (0.8) | 3.1 ± 0.3 (3.4) |
| Mitoxantrone | 5.2 ± 0.3 (1.0) | 99.8 ± 4.5 (19.2)* | 20.3 ± 1.9 (4.4)* | 4.6 ± 0.5 (0.9) | 11.5 ± 0.4 (2.2) |
| Doxorubicin | 32.0 ± 0.6 (1.0) | 48.1 ± 2.0 (1.5) | 39.0 ± 3.5 (1.2) | 20.3 ± 1.9 (0.6) | 44.6 ± 3.9 (1.4) |
| Daunorubicin | 9.5 ± 1.2 (1.0) | 17.8 ± 3.9 (1.8) | 14.1 ± 0.5 (1.5) | 12.1 ± 0.2 (1.3) | 16.3 ± 0.9 (1.7) |
↵* P < 0.01.