Apatinib inhibits glycolysis by suppressing the VEGFR2/AKT1/SOX5/GLUT4 signaling pathway in ovarian cancer cells

• DOI: 10.1007/s13402-019-00455-x
• Publication Date: 2019-07-20T00:02:31Z
• Authors: Lihua Chen; Xi Cheng; Wenzhi Tu; Zihao Qi; Haoran Li; Fei Liu; Yufei Yang; Zhe Zhang; Ziliang Wang
• Keywords: Apatinib; GLUT4; Viability assay

Apatinib is a tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor-2 (VEGFR2), and has shown encouraging therapeutic effects in various malignant tumors. As yet, however, the role of apatinib ovarian cancer remained unknown. Here, we sought to elucidate vitro vivo viability proliferation cells, as well glucose metabolism these cells. The on cell were assessed using Cell Counting Kit-8 (CCK-8) colony formation assays, respectively. expression VEGFR2/AKT1/SOX5/GLUT4 pathway proteins was Western blotting, uptake lactate production assays used detect glycolysis SOX5 exogenously over-expressed silenced cells vector shRNA-based methods, RNA analyses performed RNA-seq gene-chip-based methods. GLUT4 promoter activity dual-luciferase reporter assay. p-VEGFR2 (Tyr1175), p-AKT1 (Ser473), p-GSK3β (Ser9), xenograft tissues immunohistochemistry (IHC). We found inhibited Hey OVCA433 dose-dependent time-dependent manner. also effectively suppressed by blocking In addition, predominantly rescued inhibitory effect activating its promoter. Finally, regulated suppressing VEGFR2/AKT1/GSK3β signaling pathway. From our results, conclude suppresses inhibiting VEGFR2/AKT1/GSK3β/SOX5/GLUT4 may serve promising drug for treatment cancer.