Apatinib, a Novel Tyrosine Kinase Inhibitor, Promotes ROS-Dependent Apoptosis and Autophagy via the Nrf2/HO-1 Pathway in Ovarian Cancer Cells

Apatinib, a new-generation oral tyrosine kinase inhibitor targeting the vascular endothelial growth factor receptor 2 (VEGFR2/KDR/Flk-1) signaling pathway, shows favorable therapeutic effects in various malignant tumors. However, its effect on ovarian Cancer has not yet been characterized. Here, we demonstrated that apatinib inhibited ovarian Cancer cell growth and migration in a concentration-dependent manner. Further, we found that apatinib could directly act on tumor cells and promote ROS-dependent Apoptosis and Autophagy. Mechanistically, we showed that apatinib suppressed glutathione to generate ROS via the downregulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway and maintained an antitumor effect at a low level of VEGFR2/KDR/Flk-1 in ovarian Cancer, suggesting that combination of apatinib with Nrf2 inhibitor may be a promising therapy strategy for patients with ovarian Cancer.