Effect of nsSNP mutations on MRP1-mediated resistance to chemotherapeutic agents and metalloids in HEK293 cell lines
| Cell Line/ nsSNP | Relative Resistancea | ||||
|---|---|---|---|---|---|
| Vincristine | Doxorubicin | Etoposide | Na+ Arsenite | K+ Antimony Tartrate | |
| Wild-type | 12.2 ± 0.6 | 3.9 ± 1.6 | 7.1 ± 0.6 | 1.4; 2.2 | 5.2; 6.4 |
| R633Q | 15.3 ± 2.9 | 3.3 ± 1.0 | 5.1 ± 0.9 | ND | ND |
| G671V | 9.3 ± 2.8 | 3.4 ± 0.6 | 7.1 ± 0.7 | ND | ND |
| R723Q | 21.3 ± 7.2 | 2.5 ± 0.1 | 6.9 ± 0.5 | ND | ND |
| A989T | 4.4 ± 1.1b** | 2.5 ± 0.6 | 5.0 ± 0.9 | 1.6; 2.3 | 3.1; 3.5 |
| C1047S | 5.1 ± 0.5*** | 1.8 ± 0.2 | 4.5 ± 0.7* | 2.0; 1.8 | 2.2; 1.7 |
ND, not determined.
↵a The resistance of HEK293 cell lines expressing wild-type and mutant MRP1 proteins was determined using an MTT assay and relative resistance factors calculated by dividing the IC50 values obtained for the MRP1-expressing cells by the IC50 values obtained for control untransfected cells. Values shown are the mean (± S.D.) obtained from three independent experiments, except for Na+ arsenite and K+ antimony tartrate where the values from two independent experiments are shown.
↵b The asterisks indicate the IC50 of mutant MRP1 proteins that are significantly different from the IC50 of wild-type MRP1 (*P < 0.05;** P < 0.005; *** P < 0.001) (t test).