Combination of Ad-SGE-REIC and bevacizumab modulates glioma progression by suppressing tumor invasion and angiogenesis

Yasuhiko Hattori, Kazuhiko Kurozumi, Yoshihiro Otani, Atsuhito Uneda, Nobushige Tsuboi, Keigo Makino, Shuichiro Hirano, Kentaro Fujii, Yusuke Tomita, Tetsuo Oka, Yuji Matsumoto, Yosuke Shimazu, Hiroyuki Michiue, Hiromi Kumon, Isao Date

Research output: Contribution to journalArticlepeer-review


Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and its overexpression has been shown to exert anti-tumor effects as a therapeutic target gene in many human cancers. Recently, we demonstrated the anti-glioma effects of an adenoviral vector carrying REIC/Dkk-3 with the super gene expression system (Ad-SGE-REIC). Anti-vascular endothelial growth factor treatments such as bevacizumab have demonstrated convincing therapeutic advantage in patients with glioblastoma. However, bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. In this study, we examined the effects of Ad-SGE-REIC on glioma treated with bevacizumab. Ad- SGE-REIC treatment resulted in a significant reduction in the number of invasion cells treated with bevacizumab. Western blot analyses revealed the increased expression of several endoplasmic reticulum stress markers in cells treated with both bevacizumab and Ad- SGE-REIC, as well as decreased β-catenin protein levels. In malignant glioma mouse models, overall survival was extended in the combination therapy group. These results suggest that the combination therapy of Ad-SGE-REIC and bevacizumab exerts anti-glioma effects by suppressing the angiogenesis and invasion of tumors. Combined Ad-SGE-REIC and bevacizumab might be a promising strategy for the treatment of malignant glioma.

Original languageEnglish
Article numbere0273242
JournalPloS one
Issue number8 August
Publication statusPublished - Aug 2022

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Combination of Ad-SGE-REIC and bevacizumab modulates glioma progression by suppressing tumor invasion and angiogenesis'. Together they form a unique fingerprint.

Cite this