Apatinib inhibits pancreatic cancer growth, migration and invasion through the PI3K/AKT and ERK1/2/MAPK pathways

BACKGROUND: Pancreatic cancer is generally characterized with high levels of malignancy and poor prognosis. In addition, there are currently no effective therapeutic agents against the disease. However, apatinib which is a small molecular agent targeting the vascular endothelial growth factor receptor 2 (VEGFR-2), has been shown to generate favorable outcomes in gastric cancer. Therefore, the present study explored the effects of apatinib on pancreatic cancer. METHODS: The activity of the ASPC-1 or PANC-1 cells was examined through colony formation assays, wound healing experiments as well as the Transwell and Western blot (WB) analyses. Additionally, a xenograft model was established by subcutaneously injecting the ASPC-1 cells into nude mice. Microvessel density (MVD) and Ki-67 expression were examined through immunohistochemistry (IHC) and WB analyses. RESULTS: The findings showed that treatment with either 10 or 20 µM of apatinib led to a decrease in the proliferation, migration and invasion of ASPC-1 and PANC-1 cells. Additionally, apatinib significantly hindered xenograft growth. Moreover, there was a decrease in Ki-67 expression and MVD, 21 days after treatment with apatinib. The results also showed that apatinib had no effect on the levels of the VEGFR-2, ERK1/2 and AKT proteins although there was a significant decrease in the expression of phosphate VEGFR2 (p-VEGFR2), phosphate AKT (p-AKT) and phosphate ERK1/2 (p-ERK1/2). CONCLUSIONS: Apatinib inhibits the proliferation and migration of pancreatic cancer cells, blocking growth and angiogenesis in transplanted tumors. In addition, the underlying mechanism may involve phosphorylation of the PI3K/AKT and ERK1/2/MAPKs signaling pathways.