Inhibition of human nasopharyngeal carcinoma growth and metastasis in mice by adenovirus-associated virus–mediated expression of human endostatin
- Xiang-Ping Li1,
- Christine Y.S. Li4,
- Xiaohua Li1,
- Yanqing Ding1,
- Lally L.Y. Chan4,
- Pai-Hao Yang4,
- Gang Li1,
- Xiong Liu1,
- Jennifer S. Lin4,
- Jide Wang2,
- Mingliang He5,
- Hsiang-fu Kung5,
- Marie C. Lin4 and
- Ying Peng3
- Departments of 1Otolaryngology and 2Gastroenterology, Nanfang Hospital, Nanfang Medical University; 3Department of Neurology, The Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; 4Department of Chemistry, Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery, The University of Hong Kong; and 5Li Ka Shing Institute of Health Sciences and Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, China
- Requests for reprints: Marie C. Lin, Department of Chemistry, 8/F Kadoorie Biological Science Building, The University of Hong Kong, Pokfulam, Hong Kong, China. Phone: 852-2299-0776; Fax: 852-2817-1006. E-mail: mcllin{at}hkusua.hku.hk
Abstract
Nasopharyngeal carcinoma (NPC) is a highly malignant and frequently metastasized tumor. Endostatin has been shown to inhibit NPC growth, but its efficacy against NPC metastasis has not been shown in vivo. Here, we established a NPC metastasis model in mice by transplanting EBV-positive NPC cells, C666-1, in the livers of nude mice and observed lung metastasis. Furthermore, we showed that tail vein injection of recombinant adeno-associated virus encoding human endostatin (rAAV-hEndo) significantly prolonged the median survival rate of NPC metastasis–bearing mice (from 22 to 37 days, P < 0.01). The rAAV-hEndo treatment resulted in a statistically significant reduction in tumor growth and microvessel formation. It also increased the apoptotic index in the primary liver tumor but not in the normal liver tissue. Importantly, no formation of liver or lung metastasis was detected. The potent inhibition of NPC metastasis suggests the feasibility of combining rAAV-hEndo gene therapy with other therapies for the prevention and treatment of NPC metastasis. [Mol Cancer Ther 2006;5(5):1290–8]
Footnotes
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Grant support: The Guangdong Natural Science Fund, China (04020406, to X-P. Li and Y. Peng); the National Natural Science Fund of China (30471945 to X-P. Li); the Science and Technology Program of Guangdong province (2003c30303 to X-P. Li and Y. Peng); Li Ka Shing Institute of Health Sciences, and the Innovation and Technology Fund (ITS/084/03, H-F. Kung); this work is partially supported by the Foundation of Guangzhou Science and Technology Bureau (2005Z1-E0131 to H-F. Kung).
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted March 2, 2006.
- Received August 30, 2005.
- Revision received January 25, 2006.
- American Association for Cancer Research
