Table 1.
Combination index (CI), dose reduction index (DRI), and potentiation factor (PF), according to the different cytotoxic ratio of everolimus (EV) and 5‐aza‐2′‐deoxycytidine (AZA) combination in MZ‐CRC‐1 and TT cell lines after 6 days of treatment
| Cell line | Cytotoxic ratio | ED50 (nm) | CI50 a | DRI50 b | PFc | Interpretation | |||
|---|---|---|---|---|---|---|---|---|---|
| EV | AZA | EV | AZA | EV | AZA | ||||
| MZ‐CRC‐1 | EV‐AZA (50 : 50) | 12.4 | 35.6 | 0.2 | 4.3 | 5.9 × 102 | 1.8 | 1.1 × 103 | Strong synergism |
| EV‐AZA (25–75) | 2.1 | 1.4 × 102 | 0.1 | 8.8 | 1.0 × 102 | 10.4 | 2.8 × 102 | Strong synergism | |
| EV‐AZA (75–25) | 1.3 × 102 | 3.2 × 10−1 | 2.3 | − | − | − | − | Antagonism | |
| TT | EV‐AZA (50 : 50) | 9.2 | 3.4 × 10−1 | 1.3 | − | − | − | − | Antagonism |
| EV‐AZA (25–75) | 1.2 | 8.0 | 0.7 | 1.5 | 6.4 × 102 | 6.1 | 11 | Synergism | |
| EV‐AZA (75–25) | 91.1 | 1.2 × 10−3 | 17 | − | − | − | − | Antagonism | |
a
CI50 was calculated for 50% cell survival (ED50) by isobologram analyses performed with calcusyn software.
b
DRI was calculated in case of synergism. It represents the order of magnitude (fold) of dose reduction obtained for ED50 effect in combination setting as compared to each drug alone.
c
PF was calculated in case of synergism as the ratio between the IC50 of either everolimus or AZA alone and the IC50 of everolimus or AZA in combination setting.