Effect of the vascular endothelial growth factor expression level on angiopoietin-2-mediated nasopharyngeal carcinoma growth

Background: The overexpression of angiopoietin-2 (Ang-2) has both pro-tumorigenic and anti-tumorigenic effects. However, the mechanisms of this protein's dual effects are poorly understood, and it remains unclear how Ang-2 cooperates with vascular endothelial growth factor (VEGF). In the current study, we investigated the effects of Ang-2 overexpression on nasopharyngeal carcinoma growth in the presence of different levels of VEGF. Methods: Ang-2 was introduced into the CNE2 cell line by liposome transfection, and the expression of endogenous VEGF was inhibited by microRNA-mediated RNA interference. CNE2 cells expressing varying levels of Ang-2 and VEGF were injected subcutaneously into the flanks of nude mice. Tumor growth was measured, and vessels from the harvested tumors were analyzed. Results: The overexpression of Ang-2 had no obvious effect on CNE2 tumor growth in the presence of endogenous VEGF but significantly inhibited CNE2 tumor growth when the expression of endogenous VEGF was silenced, and the Ang-2/ VEGF ratio is negatively correlated with tumor growth. Ang-2 overexpression decreased the percentage of a-SMA-positive cells around the tumor vessels but reduced the microvessel density only in the absence of VEGF. Conclusions: Our results indicate that the effects of Ang-2 on nasopharyngeal carcinoma are highly dependent on the level of VEGF expression, Ang-2/ VEGF ratio may offer a novel therapeutic approach for treating human cancer.