[Inhibition of angiogenesis properties by SZ-21]

The aim of this study is to screen out the monoclonal antibody reactive to a kind of endothelial cell line (ECV304) from SZ-1, -2, -21, -22, -51, -65, -262 and explore its function of anti-angiogenesis. The inhibitory effects of monoclonal antibody reactive to ECV304 and human lung carcinom cells (A549) adhesion and migration to extracellular matrix proteins (i.e, fibronectin and collagen IV) were studied by ELISA, the inhibition of angiogenesis in vivo was analyzed by chick chorioallantoic membrane (CAM) assays, the percentage of apoptotic cells in A549 cells was assayed by flow cytometric Annexin-V-FITC/PI dual labeling technique. The results showed that SZ-21 exhibited inhibitory effects on human umbilical vein endothelial cell line (ECV304) and pulmonary cancer cell line (A549) adhesion and migration to extracellular matrix proteins (i.e, fibronectin and collagen IV). In addition, it disrupted ongoing angiogenesis on the chick chorioallantoic membrane (CAM) model. SZ-21 also induced apoptosis of the A549 cells. In conclusion, SZ-21 inhibits angiogenesis in vivo and in vitro by blocking integrin beta(3) and inducing apoptosis. SZ-21 recognized the sequence beta(3) 28 - 35 which is far away from the RGD ligation site on GPIIIa. Integrin may interact the extracellular matrix via recognition sites other than RGD sequence.