Panax notoginseng saponins regulate VEGF to suppress esophageal squamous cell carcinoma progression via DVL3-mediated Wnt/beta-catenin signaling

摘要

Panax notoginseng saponins (PNS) have recently attracted increasing attention for their anti-tumor activities. The aim of this study was to explore the functional role and underlying mechanisms of PNS on the progression of esophageal squamous cell carcinoma (ESCC). The mRNA levels of vascular endothelial growth factor (VEGF), beta-catenin and dishevelled-3 (DVL3) were assessed using qRT-PCR. Western blot was performed to detect the expression levels of VEGF, beta-catenin and DVL3. Cell viability and proliferation abilities were determined using MTT assay. Transwell assays were used to evaluate cell migration and invasion capacities. Our data revealed that PNS hampered the viability of ESCC cells. VEGF silencing weakened proliferation, migration and invasion in ESCC cells. Mechanistically, PNS time-dependently reduced VEGF expression and PNS hampered ESCC cell proliferation, migration and invasion through VEGF. Moreover, beta-catenin and DVL3 were upregulated in ESCC tissues and cells and positively correlated with VEGF level in ESCC tissues. VEGF regulated DVL3 via the Wnt/beta-catenin signaling pathway in ESCC cells. Furthermore, PNS repressed DVL3 expression through VEGF in ESCC cells. Our study suggested that PNS suppressed ESCC progression at least partly through repressing VEGF via the DVL3-mediated Wnt/beta-catenin signaling pathway, indicating that PNS might be promising anti-tumor agents for ESCC treatment.