Fig. 5. Niclosamide is synergistic with tyrosine kinase inhibitors and MEK inhibitor.

a Niclosamide was synergistic with tyrosine kinase inhibitors (imatinib, dasatinib, and ponatinib) and MEK inhibitor (U0126) in CML cells. Synergistic effect of the combination of niclosamide and tyrosine kinase inhibitors or MEK inhibitor in CML cells was assessed by MTS assay after incubating cells with a serially diluted mixture at a fixed ratio of the two drugs. CI is plotted against the fraction effect. The reference line indicates CI = 1. CI value below 1 indicates synergism between the two drugs. b, c Niclosamide combined with U0126 induced an enhanced apoptosis in CML cells. KBM5-T315I cells were treated with niclosamide, U0126 or the combination as indicated for 24 h, the cells were then harvested for Western blotting analysis (b) and trypan blue exclusion assay (c). Actin served as a loading control for blots above which were performed sequentially. ***P < 0.0001, compared with control, one-way ANOVA, post hoc intergroup comparisons. d, e KBM5-T315I cells (d) and normal WBC (e) were treated with control medium, niclosamide (2.0 µmol/L) combined with imatinib (0.50 µmol/L), dasatinib (0.10 µmol/L), ponatinib (0.02 µmol/L), or U0126 (20.0 µmol/L) for 24 h, followed by annexin V-FITC/PI dual staining and flow cytometer analysis