Table 1.
Drug resistance profile of wild-type and mutant BCRP
| MX | SN-38 | Dox | Rho123 | |||||
|---|---|---|---|---|---|---|---|---|
| IC50 (nM) | RR | IC50 (nM) | RR | IC50 (nM) | RR | IC50 (nM) | RR | |
| pcDNA5/FRT | 5.6 ± 0.8 | - | 1.7 ± 0.1 | - | 33.1 ± 2.2 | - | 4218 ± 400.0 | - |
| Wild-type BCRP | 51.5 ± 8.5 | 9.2 | 30.3 ± 2.0 | 17.8 | 40.9 ± 6.7 | 1.2 | 4446 ± 261.5 | 1.1 |
| P392A | 24.6 ± 3.8 | 4.4* | 13.1 ± 1.0 | 7.7* | 34.8 ± 1.7 | 1.1 | 5326 ± 414.1 | 1.3 |
| P480A | 69.4 ± 10.5 | 12.4 | 37.8 ± 1.5 | 22.2 | 29.0 ± 4.0 | 0.9 | 5107 ± 272.7 | 1.2 |
| P485A | 38.5 ± 7.0 | 6.9 | 15.9 ± 2.6 | 9.4* | 41.8 ± 5.3 | 1.3 | 3237 ± 199.5 | 0.8 |
| P501A | 40.9 ± 14.6 | 7.3 | 27.5 ± 2.4 | 16.2 | 23.2 ± 3.8 | 0.7 | 4480 ± 816.4 | 1.1 |
| P574A | 49.6 ± 12.5 | 8.9 | 32.5 ± 2.6 | 19.1 | 29.6 ± 3.5 | 0.9 | 5320 ± 419.8 | 1.3 |
| P623A | 68.4 ± 14.4 | 12.2 | 36.8 ± 2.8 | 21.6 | 37.0 ± 8.8 | 1.1 | 3302 ± 388.1 | 0.8 |
The relative resistance (RR) values represent the relative levels of resistance of the mutants compared to wild-type BCRP, and were calculated by dividing the IC50 values of wild-type and mutant BCRP by the IC50 values of the vector control. Wild-type and mutant BCRP did not confer resistance to Dox or Rho123. The IC50 values shown are means ± S.D. of three experiments. Differences in IC50 values between wild-type and mutant BCRP are statistically significant:
*
p < 0.05 by the Student’s t- test. Since the expression levels of wild-type and mutant BCRP were comparable, we did not normalize the resistance data to BCRP protein expression.