J Korean Cancer Assoc.  2000 Aug;32(4):764-774.

Antiangiogenesis Gene Therapy Using Adenovirus-mediated Antisense-VEGF in Glioblastoma Multiforme

• Im SA
• Kim JS
• Nam E
• Lee SN

Abstract

PURPOSE: Vascular endothelial growth factor (VEGF) is a major positive effector of angiogenesis. We investigated the mechanism of tumor growth inhibition by adenoviral transfer of antisense- VEGF in glioma and the role of VEGF for in vivo growth of human glioma cells according to the stage of the tumor growth.
MATERIALS AND METHODS
Replication-deficient adenoviral vector containing the VEGF cDNA in an antisense orientation (Ad5CMV-alphaVEGF) were constructed to increase the in vivo applicability of antisense sequence. The effect of Ad5CMV-alphaVEGF was studied in vitro and in vivo with human glioma cell line U-87 MG. Immunohistochemical staining of the subcutaneous tumor with anti-VEGF antibody and CD34 antibody were performed to compare VEGF protein expression and the microvessel count respectively.
RESULTS
The growth curve of U-87 MG cells treated with Ad5CMV-alphaVEGF remained as same as that of mock-infected and Ad5(dl312)-infected U-87 MG cells in vitro, suggesting that Ad5CMV-alphaVEGF does not have direct cytotoxic effect. The growth of subcutaneous human glioma xenografts was inhibited by early intratumoral injection of Ad5CMV-alphaVEGF. Immuno histochemical staining of tumors showed that VEGF protein expression and mean microvessel counts were decreased in early Ad5CMV-alphaVEGF treatment group.
CONCLUSION
The efficient down-regulation of VEGF produced by tumor cells using Ad5CMV- alphaVEGF in early stage of glioma growth has an antitumor effect in vivo through antiangiogenic mechanism.

Keyword

Antiangiogenesis; Gene therapy; Adenovirus; Vascular endothelial growth factor; Glioma

MeSH Terms

Adenoviridae
Cell Line
DNA, Complementary
Down-Regulation
Genetic Therapy*
Glioblastoma*
Glioma
Heterografts
Humans
Microvessels
Vascular Endothelial Growth Factor A
DNA, Complementary
Vascular Endothelial Growth Factor A