Cytotoxic effect induced by different drug treatments in HCT-116 cells.
| Drug Treatment Schedule | IC503-a | Statistically Significant CI (95% CL)3-b |
|---|---|---|
| Continuous treatment (6 days) | ||
| Scramble oligo | >100.0 | |
| RPR-115135 | 0.52 ± 0.05 | |
| c-myc oligo | 0.41 ± 0.15 | |
| Oligo +RPR-1151353-c | ||
| c-myc oligo +RPR-115135 | 0.009 ± 0.003 | 0.103 (0.034–0.389) |
| Scramble oligo + RPR-115135 | 0.43 ± 0.21 | N.S. |
| RPR-115135 + oligo3-d | ||
| c-myc oligo +RPR-115135 | 0.78 ± 0.11 | 1.776 (1.006–4.225) |
| Scramble oligo + RPR-115135 | 0.58 ± 0.25 | N.S. |
| Oligo +RPR-1151353-e | ||
| c-myc oligo +RPR-115135 | 0.07 ± 0.04 | 0.98 (0.720–1.006) |
| Scramble oligo + RPR-115135 | 0.41 ± 0.27 | N.S. |
↵3-a The drug concentration (millimolar concentration) was expressed as mean ± S.E. of two independent experiments performed at least in triplicate.
↵3-b To analyze the interactions between the two agents, for each tested combination of the two drugs, CI (confidence interval) values were calculated as proposed by Chou and Talalay (1977,1981), for mutually exclusive drugs: CI = (D)1/(Dx)1+ (D)2/(Dx)2, where Dx represent the estimated dose of the drug alone capable of producing the same effect of the combined drugs, as estimated from the median-effect eq. 1. In outline form, CI near to 1 indicates additivity, CI >1 indicates antagonism, CI <1 indicates synergism, CI < 0.03 indicates strong synergism. To extrapolate confidence limits [(CL), i.e. statistical significance] for CI values, we conducted a parametric bootstrapping where we assumed the distribution of parameters (m andDm) as formulated in eq. 1 to be approximately gaussian, with estimated mean and asymptotic standard error as calculated using nonlinear regression commands of SPSS software.
↵3-c Cells were treated for 24 h with 0.1 mM oligos and then for an additional 5 days with different concentrations of RPR-115135 (from 0.001 to 1.0 mM).
↵3-d Cells were treated for 24 h with different concentrations of RPR-115135 (from 0.001 to 1.0 mM) and for an additional 5 days with 0.1 mM oligos.
↵3-e Cells were treated simultaneously with 0.1 mM oligos and with different concentrations of RPR-115135 (from 0.001 to 1.0 mM) for 6 days.