The integrin inhibitor cilengitide enhances the anti-glioma efficacy of vasculostatin-expressing oncolytic virus

Kentaro Fujii, Kazuhiko Kurozumi, T. Ichikawa, M. Onishi, Y. Shimazu, J. Ishida, E. A. Chiocca, B. Kaur, Isao Date

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 U87ΔEGFR 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.

Original languageEnglish
Pages (from-to)437-444
Number of pages8
JournalCancer Gene Therapy
Volume20
Issue number8
DOIs
Publication statusPublished - Aug 2013

Fingerprint

Oncolytic Viruses
Integrins
Glioma
Therapeutics
Caspase 7
Angiogenesis Inhibitors
Cilengitide
Caspase 9
Caspase 8
Human Herpesvirus 1
Brain Neoplasms
Caspase 3
Cell Movement
Endothelial Cells
Clinical Trials
Viruses

Keywords

  • cilengitide
  • glioma
  • oncolytic viral therapy

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology

Cite this

The integrin inhibitor cilengitide enhances the anti-glioma efficacy of vasculostatin-expressing oncolytic virus. / Fujii, Kentaro; Kurozumi, Kazuhiko; Ichikawa, T.; Onishi, M.; Shimazu, Y.; Ishida, J.; Chiocca, E. A.; Kaur, B.; Date, Isao.

In: Cancer Gene Therapy, Vol. 20, No. 8, 08.2013, p. 437-444.

Research output: Contribution to journalArticle

Fujii, Kentaro ; Kurozumi, Kazuhiko ; Ichikawa, T. ; Onishi, M. ; Shimazu, Y. ; Ishida, J. ; Chiocca, E. A. ; Kaur, B. ; Date, Isao. / The integrin inhibitor cilengitide enhances the anti-glioma efficacy of vasculostatin-expressing oncolytic virus. In: Cancer Gene Therapy. 2013 ; Vol. 20, No. 8. pp. 437-444.
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