Apatinib Inhibits Proliferation and Induces Apoptosis of Acute Myeloid Leukemia Stem/Progenitor like Cell Line(kg1α cells) By Inhibition PI3K/AKT Signal Pathway

OBJIECTIVE 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 stem/progenitor like cell (kg1α) and its molecule mechanism. METHODS The kg1α 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 and 20μM apatinib. RESULTS ①After treatment with a serial of apatinib (2.5、5、10、20、40μM) on AML stem-like cell line(kg1α)for 48 and 72 hours, the cell proliferation were significantly inhibited in a dose- and time-dependent mode. For treating with 48h, the cell viability were respectively (92.32±0.82) %、 (80.59±4.95) %、 (61.75±0.47) %、 (51.51±4.10) %、 (26.42±4.20) %, and all the differences had statistical significance compared with control group, and with the 50% inhibitory concentration(IC₅₀) value of (16.98±0.08) μM; However, the viability were respectively (88.42±2.91) %、 (70.83±4.45) %、 (47.87±1.59) %、 (31.41±3.57) %、 (13.26±1.96) % for 72h, and with the 50% inhibitory concentration(IC₅₀) value of (10.05±0.08) μM .②The results of Annexin V/PI showed that various concentration of apatinib induced significantly apoptosis on kg1α cells. After the treatment of 10、20、30 and 40μM apatinib for 48 hours, the apoptosis percentage was significantly higher than control group (6.12±1.26) %, respectively (4.57±1.16) %、 (12.6±2.34) %、 (16.37±4.38) % and (19.77±2.55) % ,and the differences(except for 10μM) had clearly significance compared with control group(F=18.85,P<0.001);for 72h, the apoptosis percentage of 10、20、30 and 40μM apatinib were seperately 10.83±2.96 (%、 (15.38±2.78) %、 (24.95±2.70) % and (35.17±1.36) %, compared with untreated group (5.03±1.11) % had obviously significance(F=79.425,P<0.001). 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 and induce the apoptosis of kg1αcells. Its mechanism may be related with the PI3K/AKT signal pathway.