Figure 1.
KPT-330+CS potentiates the antitumor effect of CRM1 inhibitors ex vivo. (A-D) Cell-viability analysis using Annexin V/PI on JeKo-1 cell treated with various salicylates (AS, 2.5 mM; NaS, 3 mM; CS, 3 mM) and CRM1 inhibitors (LMB, 2 nM; KPT-185, 0.2 µM; KPT-330, 0.5 µM) in combination or as single agents. (E-F) Relative IC50 was calculated for JeKo-1 (E) and OCI-Ly1 cell lines (F). The IC50 decreased from 1.3 µM to 0.3 µM on JeKo-1 cells (E), and from 1.8 µM to 0.4 µM on OCI-Ly1 cells (F) when treated with CS 3 mM and KPT-330 at the indicated concentrations as compared with KPT-330 single-agent treatment. (G) Cell viability using Annexin V/PI analysis on cell lines from different hematologic malignancies and solid tumors treated with KPT-330 (from 0.1 µM to 0.5 µM) and CS (from 1 mM to 3 mM). Results were normalized by the respective controls. *P < .05 to P < .005; **P < .005 to P < .0005; ***P < .0005. The paired Student t test was used to compare all continuous variables. A value of P < .05 was considered statistically significant. Con, control.