Survivin is critically involved in VEGFR2 signaling-mediated esophageal cancer cell survival.

Vascular endothelial growth factor (VEGF) signaling promotes angiogenesis by stimulating the migration and proliferation of endothelial cells. The aim of this study was to investigate the expression of Survivin and VEGF receptor 1/2/3 (VEGFR 1/2/3) in esophageal carcinoma tissues (ECTs), and to explore the therapy effect of the suppression of VEGFR2 signaling. Here, we found that VEGFR2 and Survivin had high expressions and a significant correlation (r = 0.874, P < 0.002) in ECTs. Further, we found that VEGFR2 signaling could activate the AKT1/MDM2/Survivin pathway. The inhibition of VEGFR2 signaling with the XL184 treatment downregulated the phosphorylation of AKT1 and MDM2, and then, increased the activation of Caspase 3/7, resulting in the reduction of cell viability and the apoptosis of HUVECs. Additionally, in the esophageal tumor model, the tumor growth was significantly suppressed by blocking Survivin and the suppression of tumor growth was more effective in the combined treatment by blocking Survivin and Bcl-xl/Bcl-2. Our data thus revealed that Survivin in the signal downstream of VEGFR2 played an important role in esophageal cancer cell survival and might be a potential candidate target for the combined therapy for esophageal cancer.