Apatinib Enhances Chemosensitivity of FLT3-ITD Mutations acute Myeloid Leukemia Cells to Homoharringtonine Via VEGFR2 Pathway

Abstract Purpose: The significance of vascular endothelial growth factor receptor (VEGFR)-3 in numerous solid tumors and acute myeloid leukemia (AML) has been demonstrated, but Apatinib remains largely unexplored. In this study, we explored whether Apatinib combined with HHT could kill AML cell lines and its possible mechanisms. Methods: All cell lines were treated with Apatinib and HHT in different concentrations with control, Apatinib alone, HHT alone, and Apatinib combined with HHT. The changes of IC50 were measured by CCK8 assay, apoptosis rate, cell cycle, and mitochondrial membrane potential in each group were measured by flow cytometry. Finally, the possible cytotoxicity mechanism was analyzed by Western blotting. Results: Our results noted that Apatinib combined with HHT remarkably inhibited cell proliferation, reduced the capacity of colony-forming, and induced apoptosis and cell cycle arrest in AML cells. Mechanistically, Apatinib and HHT play a role as a suppressor in the expression of VEGFR2 and the downstream signaling cascades, such as the PI3K, MAPK, and Stat3 pathways. Conclusion: Our preclinical data demonstrate that Apatinib combined with HHT exerts a better anti-leukemia effect than Apatinib alone by inhibiting the VEGFR2 signaling pathway, suggesting the potential role for Apatinib and HHT in the treatment of AML.