Fig. 3

Inhibition of autophagy enhanced the anti-leukemia effect of sorafenib in FLT3-mutated leukemia cells. A Inhbition of autophagy with CQ, the anti-leukemia effect of sorafenib in both Ba/F3-ITD (w/o CQ vs. w/CQ: 40 nM, 29.0 ± 3.1% vs. 44.5 ± 2.2%, P = 0.038; 80 nM, 48.6 ± 2.9% vs. 71.5 ± 3.5%, P = 0.037) and Ba/F3-ITD + D835Y cells (w/o CQ vs. w/CQ, 500 nM, 14.3 ± 0.8% vs. 42.8 ± 2.1%, P = 0.006) was enhanced. B Western blot showed sorafenib significantly increased the expression of cleaved-caspase 3 in both Ba/F3-ITD and Ba/F3-ITD + D835Y cells after being dealt with vs. without CQ. C CQ enhanced the anti-leukemia effect of sorafenib in sorafenib-resistant primary AML cells with FLT3-ITD mutation (w/o CQ vs. w/CQ, sorafenib at 5 µM, 26.7 ± 8.2% vs. 47.8 ± 2.7%, P = 0.075; sorafenib at 10 µM, 29.0 ± 1.6% vs. 53.5 ± 4.3%, P = 0.018). D Western blot showed sorafenib significantly increased the expression of cleaved-caspase 3 in sorafenib-resistant primary AML cells with FLT3-ITD mutation (Ca #3) after being dealt with vs. without CQ. E CQ enhanced the anti-leukemia effect of sorafenib in sorafenib-resistant primary AML cells with FLT3-ITD + D835Y mutation (w/o CQ vs. w/CQ, sorafenib at 5uM, 22.6 ± 9.6% vs. 56.5 ± 5.4%, P = 0.049). F Western blot showed sorafenib significantly increased the expression of cleaved-caspase 3 in sorafenib-resistant primary AML cells with FLT3-ITD + D835Y mutation (Ca #4) after being dealt with vs. without CQ