Apatinib Inhibits Proliferation and Induces Apoptosis of Acute Myeloid Leukemia Stem/progenitor Like Cell Line (kg1α cells) and Its Mechanism

OBJECTIVE To investigate the effect of Apatinib, a small-molecule vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, on the proliferation and apoptosis of acute myeloid leukemia(AML) stem/progenitor cells and its molecule mechanism.METHODS The kg1α cells and primary CD34⁺ AML stem cells were treated with a serial of concentrations of Apatinib for 48 h and 72 h, the inhibitory ratio was measured by CCK8 assay, the apoptosis percent was measured by flow cytometry. Western bolt was used to analyzed AKT/p-AKT, p-Raf and p-PTEN expression after treatment with 0, 10, 20 μmol·L^-1 Apatinib in kg1α cells.RESULTS After treatment with a serial of Apatinib (2.5, 5, 10, 20, 40 μmol·L^-1) on AML stem-like cell line(kg1α) for 48 h and 72 h, the cell proliferation were significantly inhibited in a dose-and time-dependent mode. All the differences had statistical significance compared with control group. The results of Annexin V/PI showed that various concentration of Apatinib induced significantly apoptosis on kg1α cells. After 48 h and 72 h, all the apoptosis percentage were significantly higher than control group(P<0.01); Apatinib significantly induced apoptosis of 7 cases primary AML stem cell, the difference has statistical significance; Western blot results indicated decrease the expression of AKT/p-AKT and p-Raf, however, upregulated the level of p-PTEN.CONCLUSION Apatinib can inhibit the proliferation of AML stem/progenitor like cell line(kg1α cells) and also induce the apoptosis of kg1α and primary CD34⁺ AML stem cells. Its mechanism may be related with the PI3K/AKT signal pathway.