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ID 52796
FullText URL
Author
Fujii, K
Kurozumi, K
Ichikawa, T
Onishi, M
Shimazu, Y
Ishida, J
Chiocca, EA
Kaur, B
Abstract
Oncolytic viral (OV) therapy has been considered as a promising treatment modality for brain tumors. Vasculostatin, the fragment of brain-specific angiogenesis inhibitor-1, shows anti-angiogenic activity against malignant gliomas. Previously, a vasculostatin-expressing oncolytic herpes simplex virus-1, Rapid Antiangiogenesis Mediated By Oncolytic virus (RAMBO), was reported to have a potent antitumor effect. Here, we investigated the therapeutic efficacy of RAMBO and cilengitide, an integrin inhibitor, combination therapy for malignant glioma. In vitro, tube formation was significantly decreased in RAMBO and cilengitide combination treatment compared with RAMBO or cilengitide monotherapy. Moreover, combination treatment induced a synergistic suppressive effect on endothelial cell migration compared with the control virus. RAMBO, combined with cilengitide, induced synergistic cytotoxicity on glioma cells. In the caspase-8 and -9 assays, the relative absorption of U87 Delta EGFR cell clusters treated with cilengitide and with RAMBO was significantly higher than that of those treated with control. In addition, the activity of caspase 3/7 was significantly increased with combination therapy. In vivo, there was a significant increase in the survival of mice treated with combination therapy compared with RAMBO or cilengitide monotherapy. These results indicate that cilengitide enhanced vasculostatin-expressing OV therapy for malignant glioma and provide a rationale for designing future clinical trials combining these two agents.
Keywords
cilengitide
glioma
oncolytic viral therapy
Published Date
2013-08
Publication Title
Cancer Gene Therapy
Volume
volume20
Issue
issue8
Publisher
Nature Publishing Group
Start Page
437
End Page
444
ISSN
0929-1903
NCID
AA12570566
Content Type
Journal Article
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/52519
language
英語
Copyright Holders
© Nature Publishing Group
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Refereed
True
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