Inhibition of human nasopharyngeal carcinoma growth and metastasis in mice by adenovirus-associated virus-mediated expression of human endostatin.
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.
Li
Xiang-Ping
XP
Department of Chemistry, 8/F Kadoorie Biological Science Building, The University of Hong Kong, Pokfulam, Hong Kong, China. mcllin@hkusua.hku.hk
Li
Christine Y S
CY
Li
Xiaohua
X
Ding
Yanqing
Y
Chan
Lally L Y
LL
Yang
Pai-Hao
PH
Li
Gang
G
Liu
Xiong
X
Lin
Jennifer S
JS
Wang
Jide
J
He
Mingliang
M
Kung
Hsiang-Fu
HF
Lin
Marie C
MC
Peng
Ying
Y
D000818:Animals; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism / Q000628:therapy*; D049109:Cell Proliferation; D000229:Dependovirus / Q000235:genetics*; D043169:Endostatins / Q000235:genetics* / Q000378:metabolism; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000628:therapy*; D009336:Necrosis / Q000378:metabolism; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology
D043169:Endostatins; D042461:Vascular Endothelial Growth Factor A