The growth and metastasis of nasopharyngeal carcinoma (NPC), one of the most common cancers in southern China, is closely related to neovascularization. Here, we examined whether intra-tumoral delivery of endostatin gene could lead to long-term local expression of bioactive endostatin at therapeutic levels. We constructed a recombinant adenoviral vector carrying the human endostatin gene (Ad/hEndo), which expressed high-level endostatin protein in NPC CNE-2 cells, and significantly inhibited the proliferation and migration of vascular endothelial cells in vitro. Tumor growth and angiogenesis in NPC CNE-2 xenografted tumors were significantly inhibited after 5 courses of intra-tumoral treatment with Ad/hEndo in vivo. Endostatin mRNA in tumor tissues peaked at 1-2 days after intra-tumoral administration and disappeared within 1 week, whereas the plasma endostatin protein levels peaked at 3 days after administration and lasted 2-3 weeks. The therapeutically relevant endostatin transgene expression was achieved during the course of multiple intra-tumoral administrations with Ad/hEndo. Multiple injections with adenoviral vectors did not lead to continuous increases of adenovirus neutralizing antibodies in serum. Thus, adenovirus-mediated intra-tumoral introduction of the human endostatin gene may form a viable new treatment for NPC, although readministration every 2-3 weeks may be necessary for the best effect.
Copyright (c) 2005 Wiley-Liss, Inc.