Fig. 6: S63845 and paclitaxel synergize in cells with BAK/MCL1 complexes.

a–f After OVCAR8 (a), A2780 (b), COV362 (c), PEO1 (d), OV90 (e), and Kuramochi (f) were treated with paclitaxel in combination with S63845 at the indicated concentrations for 48 h, the percentages of sub-G1 cells were detected by flow cytometry. Right panels in a–c, combination indices (CIs) were calculated according to the method of Chou and Talalay [60] using all apoptosis data obtained from the left panels. This method calculates the CI, a parameter that indicates whether drug concentrations needed to produce a particular level of cell killing (% affected), are lower than, equal to, or greater than concentrations predicted to have additive effects. Thus, CI < 1 indicates synergy, CI = 1 indicates additivity, and CI > 1 indicates antagonism. g, h After OVCAR8 cells were treated with paclitaxel combined with navitoclax (g) or paclitaxel combined with venetoclax (h) at the indicated concentrations for 48 h, the percentages of sub-G1 cells were detected by flow cytometry. i Twenty-four hours after OVCAR8 cells were transfected with indicated siRNAs, cells were treated with navitoclax + S63845, navitoclax + paclitaxel, or S63845 + paclitaxel for 48 h, and assayed for Annexin V binding by flow cytometry. (n = 3, independent experiments, mean ± S.D.).