Table 1:
Quantification of drug synergy for two cell lines (MCF7, T-47D) when confronted to two drugs: chemotherapy (paclitaxel or doxorubicin) in combination with disulfiram. Cell lines are either naive, or evolved resistance to paclitaxel or doxorubicin. Each dose response checkerboard assay is repeated four times (batch numbers 1–4 are related to different concentrations of disulfiram, in increasing concentrations) and synergy is measured using the MUSYC software package11,12. We consider the effect of disulfiram on the EC50 (potency; log(a21): see Methods) and on maximal response (efficacy; 𝛽: see Methods)
Cell line | Drug 1 | Drug 2 | Type | Batch | Potency | Log(a21) | Efficacy | 𝛽 |
---|---|---|---|---|---|---|---|---|
| ||||||||
MCF7 | Doxo | Disu | Naive | 1 | Neutral | 0.03 (−0.27, 0.36) | Synergy | 0.05 (0.04, 0.19) |
2 | Neutral | −0.01 (−0.29, 0.29) | Neutral | −0.22 (−0.89, 0.22) | ||||
3 | Neutral | −0.14 (−0.46, 0.15) | Synergy | 0.07 (0.04, 0.22) | ||||
4 | Neutral | 0.06 (−0.32, 0.35) | Synergy | 0.05 (0.01, 0.19) | ||||
| ||||||||
MCF7 | Doxo | Disu | DoxoR | 1 | Neutral | 2.6 (−0.18, 4.76) | Synergy | 0.34 (0.24, 0.82) |
2 | Synergy | 1.5 (0.39, 2.73) | Synergy | 0.29 (0.2, 0.6) | ||||
3 | Synergy | 1.1 (0.53, 2.18) | Synergy | 0.44 (0.32, 0.8) | ||||
4 | Synergy | 4.2 (1.00, 7.06) | Synergy | 0.46 (0.32, 1.01) | ||||
| ||||||||
MCF7 | Doxo | Disu | PaclR | 1 | Neutral | 1.1 (−0.62, 2.53) | Synergy | 0.19 (0.08, 0.41) |
2 | Synergy | 1.4 (0.05, 2.66) | Synergy | 0.19 (0.11, 0.48) | ||||
3 | Neutral | 0.8 (−0.14, 2.11) | Neutral | −0.23 (−0.93, 0.3) | ||||
4 | Synergy | 1.8 (0.78, 3.76) | Antagonism | −0.28 (−0.33, −0.06) | ||||
| ||||||||
MCF7 | Pacl | Disu | Naive | 1 | Neutral | −0.2 (−0.56, 0.69) | Synergy | 0.19 (0.17, 0.22) |
2 | Neutral | 0.5 (−0.55, 3.26) | Synergy | 0.15 (0.13, 0.19) | ||||
3 | Neutral | −0.2 (−0.62, 0.51) | Synergy | 0.15 (0.13, 0.2) | ||||
4 | Neutral | −0.1 (−0.61, 0.6) | Synergy | 0.18 (0.16, 0.26) | ||||
| ||||||||
MCF7 | Pacl | Disu | PaclR | 1 | Neutral | 4.6 (−0.17, 4.59) | Synergy | 0.08 (0.05, 0.21) |
2 | Neutral | −0.6 (−4.62, 3.38) | Neutral | 0.06 (−0.03, 0.19) | ||||
3 | Neutral | 1.8 (−0.18, 5.75) | Synergy | 0.21 (0.14, 0.45) | ||||
4 | Neutral | 6.8 (0.00, 8.00) | Neutral | 0.03 (0.00, 0.13) | ||||
| ||||||||
MCF7 | Pacl | Disu | DoxoR | 1 | Neutral | −6.6 (−8.00, 0.00) | Neutral | 0.01 (−0.14, 0.07) |
2 | Neutral | 0.8 (−0.56, 1.39) | Neutral | 0.00 (−0.02, 0.08) | ||||
3 | Neutral | 0.0 (−8, 0.00) | Synergy | 0.06 (0.03, 0.1) | ||||
4 | Neutral | 7.0 (0, 7.98) | Neutral | −0.01 (−0.02, 0.08) | ||||
| ||||||||
T-47D | Doxo | Disu | Naive | 1 | Neutral | −0.2 (−0.44, 0.06) | Neutral | −0.34 (−0.48, 0.11) |
2 | Neutral | −0.3 (−0.53, 0.11) | Neutral | −0.16 (−0.98, 0.14) | ||||
3 | Neutral | −0.3 (−0.57, 0.02) | Neutral | 0.10 (−0.99, 0.16) | ||||
4 | Neutral | −0.3 (−0.60, 0.20) | Neutral | −0.09 (−0.96, 0.13) | ||||
| ||||||||
T-47D | Doxo | Disu | DoxoR | 1 | Neutral | 0.5 (−0.18, 1.47) | Synergy | 0.10 (0.04, 0.31) |
2 | Neutral | 0.3 (−0.32, 1.24) | Synergy | 0.11 (0.07, 0.26) | ||||
3 | Neutral | −0.2 (−3.96, 1.09) | Synergy | 0.21 (0.14, 0.29) | ||||
4 | Neutral | −0.1 (−4.12, 1.38) | Synergy | 0.12 (0.03, 0.21) | ||||
| ||||||||
T-47D | Doxo | Disu | PaclR | 1 | Neutral | 0.7 (−0.5, 1.82) | Neutral | 0.02 (−0.01, 0.09) |
2 | Neutral | −1.1 (−5.1, 0.71) | Neutral | 0.05 (−0.03, 0.09) | ||||
3 | Neutral | 0.3 (−0.31, 0.86) | Synergy | 0.03 (0.02, 0.08) | ||||
4 | Synergy | 0.7 (0.15, 1.26) | Synergy | 0.04 (0.02, 0.1) | ||||
| ||||||||
T-47D | Pacl | Disu | Naive | 1 | Antagonism | −0.5 (−0.82, −0.13) | Synergy | 0.05 (0.05, 0.08) |
2 | Neutral | −0.5 (−0.9, 0.24) | Synergy | 0.04 (0.03, 0.06) | ||||
3 | Neutral | −0.3 (−0.68, 0.64) | Synergy | 0.03 (0.02, 0.06) | ||||
4 | Neutral | 4.0 (0.00, 8.00) | Synergy | 0.05 (0.05, 0.08) | ||||
| ||||||||
T-47D | Pacl | Disu | PaclR | 1 | Neutral | −1.3 (−5.22, 0.9) | Neutral | −0.01 (−0.03, 0.04) |
2 | Neutral | 8.0 (0.00, 8.00) | Neutral | 0.01 (0.00, 0.06) | ||||
3 | Neutral | 8.0 (0.00, 8.00) | Neutral | 0.00 (−0.01, 0.05) | ||||
4 | Neutral | 0.5 (−3.15, 4.85) | Neutral | 0.00 (−0.01, 0.07) | ||||
| ||||||||
T-47D | Pacl | Disu | DoxoR | 1 | Neutral | −0.07 (−4.03, 2.16) | Synergy | 0.03 (0.02, 0.1) |
2 | Synergy | 6.6 (0.8, 6.35) | Neutral | 0.00 (−0.01, 0.07) | ||||
3 | Synergy | 0.8 (0.38, 1.27) | Neutral | 0.01 (−0.01, 0.07) | ||||
4 | Synergy | 2.6 (0.9, 4.94) | Neutral | 0.01 (−0.02, 0.07) |