Fig. 4

Ponatinib shows its antitumor activity by targeting multiple signaling pathways. a. CRC057, CRC119 and CRC240 were resistant to axitinib, sunitinib and dasatinib, suggesting that the mechanism of action of ponatinib in these three cell lines may be through inhibiting a common signaling pathway or pathways (one-way ANOVA, Tukey’s multiple comparison test: *, **, *** p < 0.05, the error bars represent standard deviation among replicates). b. Drug screening with the specific inhibitors of ponatinib targets. c. In vitro pre- and post-treatment western blot analysis of the intracellular tyrosine kinase domains of the ponatinib targets. D. In vitro pre- and post-treatment western blot analysis of the downstream signaling pathways of ponatinib’s targets