Oncolytic herpes virus armed with vasculostatin in combination with bevacizumab abrogates glioma invasion via the CCN1 and AKT signaling pathways

Yusuke Tomita, Kazuhiko Kurozumi, Ji Young Yoo, Kentaro Fujii, Tomotsugu Ichikawa, Yuji Matsumoto, Atsuhito Uneda, Yasuhiko Hattori, Toshihiko Shimizu, Yoshihiro Otani, Tetsuo Oka, Balveen Kaur, Isao Date

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Abstract

Anti-VEGF treatments such as bevacizumab have demonstrated convincing therapeutic advantage in patients with glioblastoma. However, bevacizumab has also been reported to induce invasiveness of glioma. In this study, we examined the effects of rapid antiangiogenesis mediated by oncolytic virus (RAMBO), an oncolytic herpes simplex virus-1 expressing vasculostatin, on bevacizumab-induced glioma invasion. The effect of the combination of RAMBO and bevacizumab in vitro was assessed by cytotoxicity, migration, and invasion assays. For in vivo experiments, glioma cells were stereotactically inoculated into the brain of mice. RAMBO was intratumorally injected 7 days after tumor inoculation, and bevacizumab was administered intraperitoneally twice a week. RAMBO significantly decreased both the migration and invasion of glioma cells treated with bevacizumab. In mice treated with bevacizumab and RAMBO combination, the survival time was significantly longer and the depth of tumor invasion was significantly smaller than those treated with bevacizumab monotherapy. Interestingly, RAMBO decreased the expression of cysteine-rich protein 61 and phosphorylation of AKT, which were increased by bevacizumab. These results suggest that RAMBO suppresses bevacizumab- induced glioma invasion, which could be a promising approach to glioma therapy.

Original languageEnglish
Pages (from-to)1418-1429
Number of pages12
JournalMolecular cancer therapeutics
Volume18
Issue number8
DOIs
Publication statusPublished - Jan 1 2019

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Oncolytic Viruses
Glioma
Cysteine-Rich Protein 61
Bevacizumab
Human Herpesvirus 1
Glioblastoma
Vascular Endothelial Growth Factor A
Neoplasms
Therapeutics
Phosphorylation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Oncolytic herpes virus armed with vasculostatin in combination with bevacizumab abrogates glioma invasion via the CCN1 and AKT signaling pathways. / Tomita, Yusuke; Kurozumi, Kazuhiko; Yoo, Ji Young; Fujii, Kentaro; Ichikawa, Tomotsugu; Matsumoto, Yuji; Uneda, Atsuhito; Hattori, Yasuhiko; Shimizu, Toshihiko; Otani, Yoshihiro; Oka, Tetsuo; Kaur, Balveen; Date, Isao.

In: Molecular cancer therapeutics, Vol. 18, No. 8, 01.01.2019, p. 1418-1429.

Research output: Contribution to journalArticle

Tomita, Yusuke ; Kurozumi, Kazuhiko ; Yoo, Ji Young ; Fujii, Kentaro ; Ichikawa, Tomotsugu ; Matsumoto, Yuji ; Uneda, Atsuhito ; Hattori, Yasuhiko ; Shimizu, Toshihiko ; Otani, Yoshihiro ; Oka, Tetsuo ; Kaur, Balveen ; Date, Isao. / Oncolytic herpes virus armed with vasculostatin in combination with bevacizumab abrogates glioma invasion via the CCN1 and AKT signaling pathways. In: Molecular cancer therapeutics. 2019 ; Vol. 18, No. 8. pp. 1418-1429.
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