Mechanisms Of Luteolin Suppresses Angiogenesis And Vasculogenic Mimicry Formation

Objective:The effects of luteolin on vascular patterns of human choroidal melanoma C918 cells were studied in vitro,and the related mechanisms were preliminarily investigated.Methods:Three-dimensional cell culture models were constructed in vitro: vascular tube formation of HUVECs,vasculogenic mimicry(VM)tube formation of choroidal melanoma C918 cells and the "Mosaic" vascular tube formation by both of them.CCK-8 was used to detect the effects of luteolin on the activity of C918 cells and HUVECs.Ed U assay,Wound-healing assay,Transwell cell migration assay and Transwell cell invasion assay were performed to examine the effects of luteolin on cell proliferation,migration and invasion capacities,respectively.The secretion of VEGF was detected by Enzyme-linked immunosorbent assay(ELISA).The expression of p-PI3 K and p-Akt proteins were detected by Western blot.Results:The CCK-8 assay results displayed that the IC50 of luteolin on C918 cells and HUVECs were 24.41 μmol/L and 27.85 μmol/L at 24 h,respectively.Ed U cell proliferation assay,Wound-healing assay and Transwell cell migration assay showed that luteolin can inhibit the proliferation and migration of C918 cells and HUVECs,and inhibitory effects were dose-dependent.Transwell cell invasion assay showed that luteolin can inhibit the invasion of C918 cells in a dose-dependent manner.ELISA showed that luteolin could inhibit VEGF secretion of C918 cells and HUVECs.Western blot showed that luteolin reduced the expression of p-PI3 K and p-Akt in C918 cells and HUVECs.Conclusion:In vitro,luteolin inhibited angiogenesis of HUVECs,vasculogenic mimicry(VM)and the "Mosaic" angiogenesis of choroidal melanoma C918 cells.Luteolin effectively inhibited the proliferation,migration,invasion of C918 cells,as well as the proliferation,migration of HUVECs.Luteolin also inhibited the secretion of VEGF and the expression levels of p-PI3 K and p-Akt in C918 cells and HUVECs.