Fig. 1

Combination effects of selinexor with chemotherapeutics. (A) Cell viability of SK-UT1 cell line treated with increasing concentrations of selinexor, eribulin and doxorubicin for 72 h. SK-UT1 cells were treated with selinexor (dose range 0.02 to 2µM) in combination with either doxorubicin (dose range 0.02 to10µM), eribulin (dose range 0.004 to 2µM) as a 5 × 5 or 6 × 6 matrix of concentrations in a cell viability assay. (B) Dose-response plots of Selinexor + doxorubicin. (C) Bliss synergy plots of Selinexor + doxorubicin. (D) Dose response plots of selinexor + eribulin. (E) Bliss synergy plots of selinexor + eribiulin. (F) Colony formation assay in SK-UT1 cells pretreated with drug as indicated for 2 weeks. (G) Apoptosis evaluation after 72 h of single-agent or combined treatment in SK-UT1 cells. 20nM selinexor, 80nM doxorubicin, 20nM. Statistical analysis was done using one-way ANOVA, and asterisks show significant differences (***P < 0.001; ****P < 0.0001). (H) Schematic of the treatment protocol. (I) Photographs of excised tumors in each group (J and K) The average tumor volume and tumor weight of SK-UT1 xenografted nude mice treated with selinexor (15 mg/kg), eribulin(1 mg/kg) and doxorubicin(4 mg/kg) either alone or in combination, for 32 days. Results are represented as the mean ± SEM of at least seven animals in each group (*P < 0.05). (L) Formalin-fixed tumor tissues were immunostained with Ki67 and XPO1 antibodies (n = 3 animals/group)