Table 3.
Effect of PF-4989216 on ABCG2-Mediated Mitoxantrone Resistance in ABCG2-Overexpressing S1-M1-80 Cells and ABCG2-Transfected R482-HEK293 Cells
| IC50a (FR)b |
|||
| drug | concentration (nM) | S1 (nM) | S1-M1-80 (μM) |
| mitoxantrone | 5.05 ± 1.13 (1.0) | 68.37 ± 3.01 (1.0) | |
| +PF-4989216 | 100 | 4.21 ± 0.87 (1.2) | 73.97 ± 4.15 (1.0) |
| +PF-4989216 | 200 | 3.67 ± 0.92 (1.4) | 79.19 ± 7.12 (0.9) |
| +Ko143 | 1000 | 4.76 ± 1.15 (1.0) | 0.29 ± 0.06***c (235.8) |
| pcDNA-HEK293 (nM) | R482-HEK293 (nM) | ||
| mitoxantrone | 1.34 ± 0.20 (1.0) | 112.78 ± 15.94 (1.0) | |
| +PF-4989216 | 100 | 1.51 ± 0.26 (0.9) | 69.01 ± 14.41* (1.6) |
| +PF-4989216 | 200 | 1.19 ± 0.23 (1.1) | 69.61 ± 12.02* (1.6) |
| +Ko143 | 1000 | 1.38 ± 0.23 (1.0) | 10.27 ± 2.17*** (11.0) |
a
IC50 values are mean ± SD calculated from dose–response curves obtained from three independent experiments using cytotoxicity assay as described in Experimental Section.
b
Abbreviation: FR, fold-reversal. FR values were obtained by dividing IC50 values of cells treated with a particular anticancer drug in the absence of an inhibitor by IC50 values of cells treated with the same anticancer drug in the presence of an inhibitor.
c*
P < 0.05
**
P < 0.01
***
P < 0.001.