IFNß sensitizes TRAILinduced apoptosis by upregulation of death receptor 5 in malignant glioma cells.
Oncol Rep
; 42(6): 2635-2643, 2019 Dec.
Article
en En
| MEDLINE
| ID: mdl-31638255
ABSTRACT
Tumor necrosis factorrelated apoptosisinducing 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 TRAILinduced apoptosis. To overcome such resistance and to improve the efficacy of TRAILbased 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 interferonß (IFNß) (with its pleiotropic antitumor activities) could sensitize malignant glioma cells to TRAILinduced apoptosis using glioma cell lines. TRAIL exhibited a dosedependent 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 IFNß (clinically relevant concentration 10 IU/ml) in A172, AM38, T98G, U138MG and U251MG demonstrated a more marked antitumor effect than TRAIL alone. Furthermore, the antitumor effect of the combined treatment with TRAIL and IFNß may be enhanced via an extrinsic apoptotic system, and upregulation of DR5 was revealed to play an important role in this process in U138MG cells. These findings provide an experimental basis to suggest that combined treatment with TRAIL and IFNß may offer a new therapeutic strategy for malignant gliomas.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
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Protocolos de Quimioterapia Combinada Antineoplásica
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Interferón beta
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Glioblastoma
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Ligando Inductor de Apoptosis Relacionado con TNF
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Receptores del Ligando Inductor de Apoptosis Relacionado con TNF
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article