Overcoming ABCG2-mediated Chemoresistance

The MDCKII cells were seeded as described in the WST-1 assay section, and treated with increasing concentrations of mitoxantrone (0.01 µM up to 50 µM) or solvent (0.1% DMSO) for 48 h. In order to detect a reversal of the ABCG2-mediated chemoresistance, novel ABCG2 interacting compounds (QCc, DMQCa, DMQCb, DMQCc, and DMQCd) were added to mitoxantrone in 1.0 µM for 48 h. Afterwards, the WST-1 assay was performed as described [37 (link)]. The left-shift factor was calculated from IC₅₀ minus SEM from the mitoxantrone alone treatment by IC₅₀ plus SEM from combined use of mitoxantrone and carborane-based derivatives (QCc, DMQCa, DMQCb, DMQCc, and DMQCd). Data were tested for normality by the Shapiro Wilk test and significant differences between the mitoxantrone treatment groups were determined by two-way ANOVA with the Holm-Šidák post hoc test using SigmaPlot 14.5. The IC₅₀ values were defined as 50% reduced cell viability and calculated with SigmaPlot 14.5 by nonlinear regression. All data were normalized against the vehicle control and were expressed as mean ± SEM, calculated from at least three independent experiments.