Antiangiogenesis Gene Therapy Using Adenovirus-mediated Antisense-VEGF in Glioblastoma Multiforme.
- Author:
Seock Ah IM
1
;
Jeong Soo KIM
;
Eunmi NAM
;
Soon Nam LEE
Author Information
1. Department of Internal Medicine, Ewha Womans University Medical College.
- Publication Type:In Vitro ; Original Article
- Keywords:
Antiangiogenesis;
Gene therapy;
Adenovirus;
Vascular endothelial growth factor;
Glioma
- MeSH:
Adenoviridae;
Cell Line;
DNA, Complementary;
Down-Regulation;
Genetic Therapy*;
Glioblastoma*;
Glioma;
Heterografts;
Humans;
Microvessels;
Vascular Endothelial Growth Factor A
- From:Journal of the Korean Cancer Association
2000;32(4):764-774
- CountryRepublic of Korea
- Language:Korean
-
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.
