IFN‑β sensitizes TRAIL‑induced apoptosis by upregulation of death receptor 5 in malignant glioma cells

Sodai Yoshimura, Emiko Sano, Yuya Hanashima, Shun Yamamuro, Koichiro Sumi, Takuya Ueda, Tomohiro Nakayama, Hiroyuki Hara, Atsuo Yoshino*, Yoichi Katayama

*この研究の対応する著者

研究成果: Article査読

5 被引用数 (Scopus)

抄録

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor (TNF) family, induces apoptosis in cancer cells by binding to its receptors, death receptor 4 (DR4) and DR5, without affecting normal cells, and is therefore considered to be a promising antitumor agent for use in cancer treatment. However, several studies have indicated that most glioma cell lines display resistance to TRAIL-induced apoptosis. To overcome such resistance and to improve the efficacy of TRAIL-based therapies, identification of ideal agents for combinational treatment is important for achieving rational clinical treatment in glioblastoma patients. The main aim of this study was to investigate whether interferon-β (IFN-β) (with its pleiotropic antitumor activities) could sensitize malignant glioma cells to TRAIL-induced apoptosis using glioma cell lines. TRAIL exhibited a dose-dependent antitumor effect in all of the 7 types of malignant glioma cell lines, although the intensity of the effect varied among the cell lines. In addition, combined treatment with TRAIL (low clinical dose: 1 ng/ml) and IFN-β (clinically relevant concentration: 10 IU/ml) in A-172, AM-38, T98G, U-138MG and U-251MG demonstrated a more marked antitumor effect than TRAIL alone. Furthermore, the antitumor effect of the combined treatment with TRAIL and IFN-β may be enhanced via an extrinsic apoptotic system, and upregulation of DR5 was revealed to play an important role in this process in U‑138MG cells. These findings provide an experimental basis to suggest that combined treatment with TRAIL and IFN-β may offer a new therapeutic strategy for malignant gliomas.

本文言語English
ページ(範囲)2635-2643
ページ数9
ジャーナルOncology Reports
42
6
DOI
出版ステータスPublished - 2019
外部発表はい

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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