Liver Cancer
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 15, 2004; 10(10): 1409-1414
Published online May 15, 2004. doi: 10.3748/wjg.v10.i10.1409
Effects of endostatin-vascular endothelial growth inhibitor chimeric recombinant adenoviruses on antiangiogenesis
Xin Pan, Yong Wang, Min Zhang, Wei Pan, Zhong-Tian Qi, Guang-Wen Cao
Xin Pan, Min Zhang, Wei Pan, Zhong-Tian Qi, Department of Microbiology, Second Military Medical University, Shanghai 200433, China
Yong Wang, Department of Ophthalmology of Changhai Hospital, Second Military Medical University, Shanghai 200433, China
Guang-Wen Cao, Department of Epidemiology, Second Military Medical University, Shanghai 200433, China
Author contributions: All authors contributed equally to the work.
Supported by The National Natural Science Foundation of China, No. 30170891 and No.39970819
Correspondence to: Xin Pan, Department of Microbiology, Second Military Medical University, Shanghai 200433, China. panxinpx@yahoo.com
Telephone: +86-21-25070314 Fax: +86-21-25070312
Received: October 8, 2003
Revised: November 29, 2003
Accepted: December 6, 2003
Published online: May 15, 2004
Abstract

AIM: To investigate the inhibitory effects of endostatin-vascular endothelial growth inhibitor (VEGI151) recombinant adenoviruses on neovascularization.

METHODS: We used recombinant adenoviruses to treat human vascular endothelial cell line ECV304, human hepatocellular carcinoma cell line HepG2, and murine fibroblast cell line L929, in order to study the chimeric gene expression in these cell lines. Chick choriallantic membrane (CAM) model, rabbit inflammatory corneal neovascularization (CNV) model, and liver cancer-bearing nude mice model were employed to investigate the negative biological effect of fusion molecules on neovascularization in vivo.

RESULTS: Western blot showed that the molecular weight of fusion protein was about 41kD after infection of ECV304, HepG2 and L929 cells with supernatant of AdhENDO-VEGI151. The fusion protein showed a specific inhibitory effect on the proliferation of ECV304 cells, but no inhibitory effect on the growth of HepG2 and L929 cells (F = 13112.13, P = 0.0001). In the chick choriallantic membrane (CAM) assay, the expressed fusion protein significantly inhibited neovascularization. Rabbit inflammatory corneal neovasculari-zation (CNV) induced by intrastromal sutures resulted in a uniform neovascular response. In this model, direct subconjunctival injection of AdhENDO-VEGI151 expressed the fusion protein in vivo and suppressed the development of CNV. Topical application of AdhENDO-VEGI151 led to a significant suppression of CNV (F = 1413.11, P = 0.0001), as compared with the control group of AdLacZ. Immunohist-ochemical staining showed the fusion protein dominantly expressed in corneal epithelium. Compared with the control group of AdLacZ (4075.9 ± 1849.9 mm3), the average tumor size of group AdhENDO-VEGI151 reduced in size (487.7 ± 241.2 mm3) (F = 14.80, P = 0.0085), with an inhibition rate of 88.03%. Immunohistochemical staining showed the adenoviruses carried the fusion gene expressed on liver cancer cell membrane. MVD decreased more significantly in treated mice (30.75% ± 3.31%) than in AdLacZ control (50.25% ± 8.65%) (F = 17.72, P = 0.0056) with an inhibition rate of 39%.

CONCLUSION: Fusion protein expressed by recombinant adenoviruses has a significant inhibitory effect on neovasculari-zation.

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