Table 2.
Effect of FTC on the SN‐38 and mitoxantrone resistance of mutant BCRP transfectants
| Cell line | SN‐38 | Mitoxantrone | Relative expression level of total BCRP§ | ||||
|---|---|---|---|---|---|---|---|
| Degree of resistance† | RI‡ | Degree of resistance† | RI‡ | ||||
| −FTC | +FTC | −FTC | + FTC | ||||
| PA317 | 1.0 ± 0.1 | 0.9 ± 0.1 | – | 1.0 ± 0.1 | 0.9 ± 0.1 | – | – |
| PA/WT‐mix | 19.3 ± 1.7 | 1.4 ± 0.1 | 13.8 | 9.0 ± 0.3 | 1.2 ± 0.1 | 7.5 | 100 |
| PA/C592S‐cl.6 | 4.2 ± 0.3 | 1.2 ± 0.1 | 3.5 | 3.7 ± 0.1 | 1.3 ± 0.1 | 2.8 | 52 |
| PA/C603S‐cl.3 | 106 ± 7.3 | 7.9 ± 0.3 | 13.4 | 57 ± 5.9 | 15 ± 0.7 | 3.8 | 146 |
| PA/C603S‐cl.7 | 18 ± 2.0 | 4.1 ± 0.2 | 4.4 | 28 ± 3.9 | 12 ± 1.0 | 2.3 | 135 |
| PA/C592S·C608S‐cl.7 | 8.4 ± 0.5 | 4.0 ± 0.2 | 2.1 | 3.3 ± 0.2 | 3.3 ± 0.1 | 1.0 | 151 |
| PA/C592S·C603S·C608S‐cl.7 | 4.1 ± 0.3 | 4.6 ± 0.3 | 0.9 | 7.5 ± 0.2 | 6.0 ± 0.8 | 1.3 | 145 |
†The cells were incubated for 4 days at 37°C in the presence or absence of various concentrations of anticancer agents in the presence or absence of 1 μM fumitremorgin C (FTC). The IC50 value (the drug dose causing a 50% inhibition of cell growth) was determined from growth inhibition curves, and the degree of resistance (x‐fold) was calculated by dividing the IC50 values of the breast cancer resistance protein (BCRP) transfectants by those of the parental PA317 cells. ‡The reversal index (RI) was determined by dividing the degree of resistance in the absence of FTC by the degree of resistance in the presence of FTC. Data are the mean ± SD of triplicate determinations. §Each total BCRP (75‐ and 70‐kDa) band intensity was measured (Fig. 3), and the relative expression levels were calculated by dividing BCRP expression values in each cell line as compared with PA/WT‐mix cells.