In conclusion, we showed that C-VGB3, which reproduces a binding region of VEGFB, could interfere with the interaction between VEGFA and VEGFR2 and inhibit angiogenesis and tumor growth via suppression of PI3K/AKT/mTOR and PLCγ/ERK1/2 pathways in both endothelial and tumor cells. Here, VEGFB is linked to neoplasm.