Isoimperatorin Inhibits Angiogenesis by Suppressing VEGFR2 Signaling Pathway.

Abstract

Angiogenesis involves in many pathological processes, including tumor metastasis, diabetic retinopathy, and rheumatoid arthritis. Therefore, identifying therapeutic drugs that target angiogenesis may be a promising strategy for disease treatment. Isoimperatorin is a furanocoumarin with anti-inflammatory and anti-microbial effects. However, the impacts of isoimperatorin on angiogenesis and its underlying mechanisms remain unclear. This study aimed to verify its effects on vascular endothelial growth factor (VEGF)-induced endothelial angiogenesis. We employed various assays including 5-ethynyl-2'-deoxyuridine incorporation assay, transwell migration assay, wound healing assay, tube formation assay, and Western blot to evaluate the effects of isoimperatorin on angiogenesis in vitro. Additionally, we utilized Western blot and immunofluorescence analysis to examine the activation of vascular endothelial growth factor receptor (VEGFR) 2 and its downstream signaling pathways following isoimperatorin treatment. To further validate the anti-angiogenic effects of isoimperatorin in vivo, we conducted a matrigel plug assay and established an orthotopic tumor model. We demonstrated that pretreatment with isoimperatorin inhibited VEGF-induced endothelial cell proliferation, migration, and tube formation. Isoimperatorin also suppressed angiogenesis in vivo in a matrigel plug assay and in an orthotopic tumor model. Our results revealed that isoimperatorin exhibited anti-angiogenic effects via inhibiting VEGFR2 and its downstream signaling pathways activation. Our study showed that isoimperatorin suppressed angiogenesis by targeting the VEGFR2 signaling pathway and could be a potential therapeutic agent for targeting angiogenesis.