TABLE 1.
PARP1 and CHK1 inhibitors synergize to kill mammary carcinoma cells
BT549 cells were plated as single cells in sextuplicate. Twelve hours after plating, cells were treated with AZD7762 (25–75 nM), UCN-01 (20–60 nM), or AZD2281 (500–1500 nM) as indicated in this table. Forty-eight hours after treatment the media was removed and replaced with drug-free media. Colonies were permitted to form for 10 days after which colonies were fixed and stained. A group of >50 cells was defined as a colony. An assessment of drug interaction was made using the CalcuSyn for Windows program. A combination index <1.00 was indicative of a synergistic drug interaction.
| Fa | CI | |
|---|---|---|
| AZD2281/AZD7762 | ||
| 500 nM/25 nM | 0.09 | 0.49 |
| 1000 nM/50 nM | 0.22 | 0.37 |
| 1500 nM/75 nM | 0.37 | 0.28 |
| AZD2281/UCN-01 | ||
| 500 nM/20 nM | 0.16 | 0.38 |
| 1000 nM/40 nM | 0.29 | 0.25 |
| 1500 nM/60 nM | 0.38 | 0.24 |
Fa, fraction affected; CI, combination index.