Table 1.
Heat map of the effects of RM and DOX at different combination ratios and regimen.
| Drug Combination | Combination Ratio (nM) | n | CI values at | |||
|---|---|---|---|---|---|---|
| IC50 | IC75 | IC90 | IC95 | |||
| RM + DOX | 1:100 | 5 | 0.956 ± 0.064 | 0.886 ± 0.047 | 0.884 ± 0.111 | 0.917 ± 0.156 |
| RM + DOX | 1:80 | 3 | 1.111 ± 0.093 | 0.913 ± 0.047 | 0.777 ± 0.056 | 0.712 ± 0.085 |
| RM + DOX | 1:60 | 3 | 1.202 ± 0.115 | 1.011 ± 0.075 | 0.877 ± 0.054 | 0.810 ± 0.065 |
| RM + DOX | 1:50 | 5 | 0.806 ± 0.069 | 0.685 ± 0.044 | 0.609 ± 0.036 | 0.575 ± 0.041 |
| RM + DOX | 1:40 | 3 | 0.856 ± 0.041 | 0.691 ± 0.048 | 0.580 ± 0.061 | 0.524 ± 0.071 |
| RM + DOX | 1:20 | 3 | 1.160 ± 0.075 | 0.942 ± 0.047 | 0.780 ± 0.033 | 0.692 ± 0.032 |
| RM → DOX | 1:100 | 6 | 2.372 ± 0.220 | 1.601 ± 0.156 | 1.105 ± 0.121 | 0.870 ± 0.105 |
| RM → DOX | 1:20 | 4 | 1.414 ± 0.094 | 1.173 ± 0.087 | 1.004 ± 0.132 | 0.918 ± 0.162 |
| DOX → RM | 100:1 | 5 | 1.622 ± 0.221 | 1.545 ± 0.209 | 1.557 ± 0.311 | 1.620 ± 0.427 |
| DOX → RM | 20:1 | 3 | 2.543 ± 0.429 | 2.273 ± 0.288 | 2.074 ± 0.263 | 1.974 ± 0.319 |
The effects on cell viability were determined using an MTT cytotoxicity assay after 72 h, and the combination index (CI) values were calculated using CompuSyn software. To determine the combination ratio and schedule of administration that yield the greatest synergistic effect, a heat map was generated, with the red color highlighting the lowest CI values signifying synergism, white highlighting values near 1 signifying additivity, and blue highlighting values greater than 1 signifying antagonism. RM + DOX indicates simultaneous administration, RM → DOX indicates pre-exposure to RM for 24 h followed by DOX for 48 h and DOX → RM indicates the reverse order. n is the number of independent trials. Each trial consisted of single drug controls and their combination. The CI values are mean ± SEM of n trials.