*4.11. Statistics*

All the experiments were performed for a minimum of three times. Data for each group are indicated as the mean ± standard deviation (SD). The results were considered statistically significant at *p* < 0.05. CompuSyn Version 1.0 (CompuSyn Inc., New York, NY, USA), based on the Chou–Talalay algorithm [43] was used to calculate the values of CI at each molar ratio of Dox and MK-2206. The combinations of the drugs indicated above that yielded CI values < 1 were considered as synergistic [44,45]. The degree of combination effects were also quantified by using R-package of the computational tool SynergyFinder (https://bioconductor.org/packages/release/bioc/html/synergyfinder. html) [46]. Zero potency interaction (ZIP) reference model was used to calculate synergy. Average delta score over a dose–response matrix was used as a summary interaction score for a drug combination. Value of delta score >0, =0 or <0 corresponds to the synergy, zero interaction and antagonism, respectively [46]. Means of normalized protein levels were compared by using the analysis of variance (ANOVA) with subsequent pairwise comparisons (Tukey HSD test) in R software (R Foundation for Statistical Computing, Vienna, Austria; URL https://www.R-project.org/).
