Inhibition of angiopoietin-1 expression in tumor cells by an antisense RNA approach inhibited xenograft tumor growth in immunodeficient mice

Angiopoietin-I (Ang I) is an angiogenic growth factor that functions through activation of its endothelium-specific tyrosine kinase receptor Tie2; it mediates the interaction between endothelial and surrounding cells to promote the remodeling, maturation and stabilization of blood vessels. Although Ang I is expressed constitutively in many adult tissues, its role in tumor growth and metastasis is not clear. Here we describe experiments in which Ang I expression was inhibited in HeLa cells by an antisense RNA approach. The modified HeLa cells produced significantly less AngI protein both in cultured cells and in tumors formed when these cells were injected into immunodeficient mice. The AngI antisense tumors grew much more slowly, with significantly reduced tumor angiogenesis compared with control tumors. Furthermore, they also had substantially increased tumor cell apoptosis and decreased tumor necrosis. Our results indicate that the perturbation of AngI expression in tumors could be an effective method to control tumor growth by inhibiting tumor angiogenesis and that antisense RNA is an efficient way to inhibit AngI protein production in tumor cells. (C) 2001 Wiley-Liss, Inc.