Mitofusin-2 is a novel anti-angiogenic factor in pancreatic cancer

Abstract

Background: Aberrant expression of mitofusin-2 (MFN2) has been found to be associated with vascular endothelial growth factor A (VEGFA)-mediated angiogenesis in human umbilical vein endothelial cells (HUVECs). This study aimed to investigate the expression of MFN2 in pancreatic cancer (PC) and the role of MFN2 in vascular endothelial cell growth and angiogenesis. Methods: Protein and mRNA expression of MFN2 and VEGFA were measured. The CCK-8 assay, tube formation assay, flow cytometry, and transmission electron microscopy were used to examine the effects of MFN2 overexpression on HUVEC growth, angiogenesis, and apoptosis. Western blot and immunocytochemical staining were conducted to measure alterations in cell cycle and apoptosis regulators and vascular endothelial growth factor receptor 2 (VEGFR2), angiopoietin-1 gene (ANGPT1), and tissue inhibitor of metalloproteinase 1 (TIMP1) expression in HUVECs. Results: The results showed that MFN2 levels were significantly decreased in tumor tissues. Contrasting results were observed for VEGFA mRNA levels. MFN2 overexpression inhibited cell growth while promoting the formation of apoptotic bodies in HUVECs. Additionally, MFN2 overexpression enhanced the protein expression of p21 and p27 while attenuating the expression of proliferating cell nuclear antigen, VEGFA, VEGFR2, ANGPT1, and TIPM1 in HUVECs. Conclusions: In conclusion, MFN2 expression negatively correlates with VEGFA expression in PC and inhibits endothelial cell growth and angiogenesis.