title: Adenovirus-mediated intra-tumoral delivery of the human endostatin gene inhibits tumor growth in nasopharyngeal carcinoma.
abstract: 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.
authors.affiliation: State Key Laboratory for Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Ran-Yi
authors.initials: RY
authors.lastname: Liu
authors.forename: Jia-Ling
authors.initials: JL
authors.lastname: Huang
authors.forename: Qi-Cai
authors.initials: QC
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Pei-Hong
authors.initials: PH
authors.lastname: Wu
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
mesh_terms: D000256:Adenoviridae; D000818:Animals; D002277:Carcinoma / Q000098:blood supply / Q000235:genetics* / Q000628:therapy*; D018450:Disease Progression; D043169:Endostatins / Q000235:genetics* / Q000627:therapeutic use*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009303:Nasopharyngeal Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000628:therapy*; D019076:Transgenes; D014407:Tumor Cells, Cultured
chemical_list: D043169:Endostatins