RESUMO
Aim To investigate the effects of isoliquiri-tigenin ( ISL) on anti-angiogenesis both in vitro and in vivo and its mechanisms. Methods We assessed the antiangiogenic activities of ISL on proliferation viabili-ty, migration and tube formation of human microvascu-lar endothelial cell line-1 (HMEC-1) in vitro. The cell proliferation viability was assessed using the Sulforho-damine B ( SRB ) assay. Modified Boyden Transwell chamber assay was done to study the effect of ISL on HMEC-1 cells migration. 2′, 7′-dichlorofluorescein di-acetate ( DCFH-DA) was used to measure the levels of intracellular reactive oxygen species ( ROS ) , which was induced by VEGF. Metalloproteinase-2 ( MMP-2 ) and metalloproteinase-9 ( MMP-9 ) expressions by HMEC-1 cells were assessed through gelatin zymogra-phy assay. HMEC-1 cells cycle was detected by flow cytometry. Moreover, we investigated the in vivo anti-angiogenic activity of ISL on chicken embryos nap al-lantoic membrane model ( CAM ) . Results ISL con-centration-dependently inhibited the growth of HMEC-1 cells as well as SW620 and A549 cells. ISL signifi-cantly and concentration-dependently suppressed the migration activity of HMEC-1 cells. Tube sample struc-ture formation further confirmed the effect of ISL on an-ti-angiogenesis. Moreover, ISL also inhibited intracel-lular ROS level, MMP-2 and MMP-9 expression by HMEC-1 cells. ISL induced endothelial cell apoptosis at a low concentration ( ISL 12 . 5 μmol · L-1 ) and blocked the cells in S phase of mitosis at higher con-centrations ( ISL 25~100 μmol·L-1 ) . Furthermore, ISL distinctly inhibited the angiogenesis of chick em-bryos in vivo. Conclusions ISL has anti-tumor and angiogenesis effects on HMEC-1 cells. The mechanism may be related to intracellular ROS scavenging and ap-optosis induction of HMEC-1 cells.