Table 2.
Combined inhibition of PARP and ATR synergistically potentiates the anti-proliferative effects of DS-8201 against HER2-positive cancer cells
| Drugs | IC50 (ng/mL) | |||||
|---|---|---|---|---|---|---|
|
| ||||||
| NCI-N87 | BT-474 | SK-BR-3 | Calu-3 | MDA-MB-453 | MDA-MB-231 | |
| DS-8201 | 54.7±19.7 | >3000 | 15.0±0.3 | 68.4±3.1 | 27.5±13.1 | >3000 |
| + 3 μM AZD2281 | 15.7±2.9 (3.5)a | >3000 (N/A) | 7.6±0.2 (2.0) | 34.8±0.4 (2.0) | 6.1±2.7 (4.5) | >3000 (N/A) |
| + 10 nM BAY1895344 | 24.9±7.5 (2.2) | >3000 (N/A) | 5.3±0.2 (2.8) | 41.8±4.4 (1.6) | 9.0±1.6 (3.0) | >3000 (N/A) |
| + 3 μM AZD2281+10 nM BAY1895344 | 8.1±1.3 (6.7) | 7.6±1.7 (N/A) | 0.7±0.5 (21.4) | 15.1±1.5 (4.5) | 5.1±1.0 (5.4) | >3000 (N/A) |
IC50 values were determined by sulforhodamine B assay in cells treated with different concentrations of drugs for 120 h. Data are presented as means ± S.D. of three independent experiments.
a
Value in parentheses indicates fold-sensitization, determined as IC50 (combination)/IC50 (DS-8201 alone).