Table 1.
Combination index (CI) and dose reduction index (DRI) values for valproic acid (VPA), simvastatin (SIM) and docetaxel (DTX) combinations accordingly to different treatment schedules
| Cell Lines | VPA + DTX | SIM + DTX | VPA + SIM + DTX | VPA + SIM→DTX | DTX→ VPA + SIM |
|---|---|---|---|---|---|
| PC3 |
aCI50: 0.930.05 bDRI50VPA:1.4 ± 0.07 DRI50 DTX: 4.7 ± 0.94 |
CI50: 0.95 ± 0.06 DRI50SIM:1.42 ± 0.13 DRI50 DTX:4.8 ± 2.8 |
CI50: 0.71 ± 0.06 DRI50 VPA:3.1 ± 0.05 DRI50 SIM:3.8 ± 1.7 DRI50 DTX: 10.9 ± 2.55 |
CI50: 0.62 ± 0.17 DRI50 VPA:4.06 ± 1.89 DRI50 SIM:3.49 ± 1.0 DRI50 DTX: 18.4 ± 4.4 |
CI50: 0.54 ± 0.06 DRI50 VPA: 5.3 ± 0.6 DRI50 SIM: 3.9 ± 0.5 DRI50 DTX: 10.2 ± 2.76 |
| 22Rv1 |
CI50: 0.7 ± 0.09 DRI50 VPA: 2.3 ± 0.55 DRI50 DTX: 3.07 ± 0.9 |
CI50: 0.55 ± 0.13 DRI50 SIM:2.9 ± 0.4 DRI50DTX:4.2 ± 1.75 |
CI50: 0.48 ± 0.1 DRI50 VPA:6.0 ± 1.5 DRI50 SIM:5.4 ± 1.9 DRI50 DTX: 7.3 ± 0.22 |
CI50: 0.55 ± 0.13 DRI50 VPA:2.3 ± 0.5 DRI50 SIM:4.05 ± 1.82 DRI50 DTX: 4.05 ± 1.82 |
CI50: 0.48 ± 0.1 DRI50 VPA: 6.0 ± 1.5 DRI50 SIM: 5.4 ± 1.9 DRI50 DTX: 9.8 ± 4.3 |
| DU145 |
CI50: 0.87 ± 0.14 DRI50 VPA:1.9 ± 0.2 DRI50 DTX: 3.9 ± 0.5 |
CI50: 0.86 ± 0.2 DRI50SIM:2.42 ± 01.2 DRI50DTX:2.54 ± 0.2 |
CI50: 0.65 ± 0.03 DRI50 VPA:2.84 ± 0.1 DRI50 SIM:6.46 ± 2.3 DRI50 DTX: 6.99 ± 0.6 |
CI50: 0.64 ± 0.04 DRI50 VPA:0.45 ± 0.07 DRI50 SIM:5.65 ± 2.05 DRI50 DTX:18.3 ± 0.03 |
CI50: 0.84 ± 0.02 DRI50 VPA: 2.32 ± 0.03 DRI50 SIM: 5.35 ± 0.07 DRI50 DTX: 4.33 ± 0.38 |
| DUR80 |
CI50: 0.67 ± 0.15 DRI50 VPA:1.9 ± 0.6 DRI50 DTX: 6.59 ± 0.8 |
CI50: 0.54 ± 0.2 DRI50SIM:53.9 ± 14.5 DRI50DTX:2.02 ± 0.7 |
CI50: 0.67 ± 0.02 DRI50 VPA:2.02 ± 0.2 DRI50 SIM:194.5 ± 20 DRI50 DTX: 7.3 ± 1.9 |
CI50: 0.51 ± 0.25 DRI50 VPA:2.5 ± 1.4 DRI50 SIM:216.1 ± 0.07 DRI50 DTX:19.9 ± 0.05 |
CI50: 0.65 ± 0.02 DRI50 VPA: 2.21 ± 0.01 DRI50 SIM: 179.6 ± 0.14 DRI50 DTX: 4.49 ± 0.62 |
Cell growth assessment was done by sulforhodamine B colorimetric assay (see Methods). aCIs values (mean ± S.D.) from at least three separate experiments performed in quadruplicate) computed at 50% of cell kill (CI50) by CalcuSyn software (Biosoft,Cam- bridge, UK). CIs smaller than 0.8 indicate strong synergism; CIs smaller than 0.9 indicate sinergysm; additivity between 0.9 and 1.2 or antagonism more than. Equipotent doses (50:50 cytotoxic ratio) of each of the two agents were evaluated after 96 h with a simultaneous (VPA + DTX: SIM + DTX or VPA + SIM + DTX) or sequential exposure with 24 h delay to either drug (VPA + SIM → DTX; DTX → VPA + SIM) as described in Methods section
bDRI values (mean ± S.D.) from at least three separate experiments performed in quadruplicate) represent the order of magnitude (fold) of dose reduction obtained for IC50 (DRI50) in combination setting compared with each drug alone