Objectives: XIAP-associated factor 1 (XAF1) is a tumor suppressor gene, but its role in angiogenesis is unknown. We investigated whether XAF1 has any antiangiogenesis effect. Methods: MS1 (a mouse endothelial cell line) was infected with an adenoviral vector ZD55-XAF1. Controls were uninfected or infected with ZD55-EGFP. Wound healing assay and tube formation assay were used to assess angiogenesis. Cell proliferation was detected by WST-1 assay, and apoptosis was detected by TUNEL and APOPercentage (TM) assays. Results: ZD55-XAF1 significantly upregulated XAF1, which was associated with decreased cell proliferation, migration and tube formation of MS1 cells. Ectopic overexpression of XAF1 induced apoptosis in MS1 and also sensitized cells to 5-fluorouracil-induced apoptosis. A significant decrease in the expression of Tie-1, Ang-1, Ang-2 and c-Myc was observed. Conclusions: Our data suggest that XAF1 possesses a potential antiangiogenesis effect. Suppressed expression of Tie-1, Ang-1, Ang-2 and c-Myc may be mechanistically responsible for the observed antiangiogenesis effect. Copyright (C) 2008 S. Karger AG, Basel.