Open Access

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

  • Authors:
    • Sodai Yoshimura
    • Emiko Sano
    • Yuya Hanashima
    • Shun Yamamuro
    • Koichiro Sumi
    • Takuya Ueda
    • Tomohiro Nakayama
    • Hiroyuki Hara
    • Atsuo Yoshino
    • Yoichi Katayama
  • View Affiliations

  • Published online on: October 22, 2019     https://doi.org/10.3892/or.2019.7383
  • Pages: 2635-2643
  • Copyright: © Yoshimura et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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December-2019
Volume 42 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yoshimura S, Sano E, Hanashima Y, Yamamuro S, Sumi K, Ueda T, Nakayama T, Hara H, Yoshino A, Katayama Y, Katayama Y, et al: IFN‑β sensitizes TRAIL‑induced apoptosis by upregulation of death receptor 5 in malignant glioma cells. Oncol Rep 42: 2635-2643, 2019
APA
Yoshimura, S., Sano, E., Hanashima, Y., Yamamuro, S., Sumi, K., Ueda, T. ... Katayama, Y. (2019). IFN‑β sensitizes TRAIL‑induced apoptosis by upregulation of death receptor 5 in malignant glioma cells. Oncology Reports, 42, 2635-2643. https://doi.org/10.3892/or.2019.7383
MLA
Yoshimura, S., Sano, E., Hanashima, Y., Yamamuro, S., Sumi, K., Ueda, T., Nakayama, T., Hara, H., Yoshino, A., Katayama, Y."IFN‑β sensitizes TRAIL‑induced apoptosis by upregulation of death receptor 5 in malignant glioma cells". Oncology Reports 42.6 (2019): 2635-2643.
Chicago
Yoshimura, S., Sano, E., Hanashima, Y., Yamamuro, S., Sumi, K., Ueda, T., Nakayama, T., Hara, H., Yoshino, A., Katayama, Y."IFN‑β sensitizes TRAIL‑induced apoptosis by upregulation of death receptor 5 in malignant glioma cells". Oncology Reports 42, no. 6 (2019): 2635-2643. https://doi.org/10.3892/or.2019.7383