Fig. 3
Effects of selinexor in combination with standard chemotherapy in vitro. a Four different triple-negative breast cancer cell lines were treated with selinexor in combination with paclitaxel, doxorubicin, gemcitabine, carboplatin, and eribulin. Cell growth was measured after 72 hours of treatment using the Sulforhodamine B (SRB) assay, and the combination index (CI) was then calculated using the method of Chou and Talalay [20]. A CI value <0.8 indicates synergism, a value equal to 1 indicates addition, and a CI significantly >1.2 indicates antagonism. b, c SUM-159PT cells were trypsinized, counted, and plated at a density of 2 × 103 cells in 60-mm plates in triplicate for each treatment group. Cells were treated for 2 weeks with vehicle, selinexor (50 nM), paclitaxel (0.5 nM), or eribulin (1 nM) or in combinations of selinexor with paclitaxel and selinexor with eribulin. Colonies were then fixed and stained with crystal violet. Percent surface area was calculated using NIH Image J v.1.48 software. Values are presented as mean ± SEM (*P < 0.005 vs control, **P < 0.001 combination paclitaxel vs selinexor alone, P = 0.0013 combination eribulin vs selinexor alone). d, e SUM-159PT cells were treated with 0.5 nM paclitaxel alone, 400 nM selinexor alone, and the combination of both. After 72 hours, annexin-V-positive cells were determined by fluorescence-activated cell sorting FACS analysis. (*P < 0.001 selinexor alone vs vehicle control, **P = 0.004 combination vs selinexor alone). Each individual experiment was performed in triplicate. DMSO dimethyl sulfoxide, FITC, fluorescein isothiocyanate