Fig. 2

Combinations of different kinase inhibitors show synergistic effects in drug-sensitive and –resistant melanoma cells. a A375 cells were treated for 72 h with BRAF inhibitors Vemurafenib or Dabrafenib alone or in combination with MK-1775 (Wee1i), AZD7762 (Chki), Danusertib (Aurki) or AZD8330 (MEKi) and cell viability was assessed. A dose-effect analysis of the drug combinations to determine synergism/antagonism based on the Chou-Talalay method was performed using the Compusyn software. Combination index (CI) values shown above the bars were mostly < 1 indicating a synergistic effect of both drugs at the specific concentrations. CI values > 1 (marked in red), indicate antagonism; white bars show BRAFi treatment alone, grey bars show the tested kinase inhibitor alone and black bars show the combined drugs. Red arrows pinpoint the most effective combinations. One representative experiment of at least 3 is shown. b Chki and Wee1i act synergistically on parental and BRAFi-resistant A375 cells. Parental and resistant A375 cells (-XP: Vemurafenib-resistant; -GP: Dabrafenib-resistant) were treated for 72 h with the indicated concentrations of 2 Chki (AZD7762 or CHIR-124) and a Wee1i (MK-1775) and cell viability was assessed. Synergy scores were calculated using the Synergyfinder software. ZIP Synergy scores > 0 indicate synergism (red regions) and scores < 0 indicate antagonism (green regions). Concentrations marked with green boxes on the x and y-axis indicate the concentrations encompassing the region of highest synergy (indicated by the white rectangle). The value in the white box represents the averaged synergy score for the region of highest synergy. One representative experiment of at least 4 is shown