Adenovirus-mediated intra-tumoral delivery of the human endostatin gene inhibits tumor growth in nasopharyngeal carcinoma.
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.
Li
Li
L
State Key Laboratory for Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China.
Liu
Ran-Yi
RY
Huang
Jia-Ling
JL
Liu
Qi-Cai
QC
Li
Yan
Y
Wu
Pei-Hong
PH
Zeng
Yi-Xin
YX
Huang
Wenlin
W
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
D043169:Endostatins