Breast cancer is a leading cause of cancer-related death in the women worldwide. Apatinib is a novel tyrosine kinase inhibitor that selectively binds and inhibits vascular endothelial growth factor receptor 2 (VEGFR-2). The clinical trials have demonstrated the objective efficacy of Apatinib against metastatic breast cancer. However, the underlying mechanism is not well established. In the present study, the breast cell lines, BT-474 and MCF-7, were investigated. The effect of Apatinib on the cell viability was determined using CCK-8 assay. The migration, invasion, cell cycle distribution and the downstream signaling of VEGFR-2 in the cells were determined after 48 h treatment with this drug. Subsequently, Vector of angiomotin (AMOT) cDNA was transfected into MCF-7 cells. The cells were either exposed to Apatinib or vehicle and then examined for cell viabilities, migration, invasion, cell cycle distribution and the downstream signaling of VEGFR-2. Apatinib demonstrated a dose-dependent, significant inhibition of cell viabilities, migration and invasion of BT-474 and MCF-7 cells, with an increase in the percentage of cells in G1 phase and a decrease in S phase. In addition, in MCF-7 cells, Apatinib decreased AMOT expression, accompanied with the decreased expression of LATS1/2, YAP, ERK1/2 phosphorylation and cyclin D1. The inhibitory effect of Apatinib on the cell activities and protein expressions were significantly suppressed by AMOT overexpression. The results of this study indicated that Apatinib inhibited MCF-7 cell proliferation and invasion through AMOT/VEGFR-2 pathway.
Keywords: Apatinib; Breast cancer; Yes-associated protein; invasion; proliferation.