Ionizing radiation enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through up-regulations of death receptor 4 (DR4) and death receptor 5 (DR5) in human osteosarcoma cells

Despite improvements in chemotherapy and surgery in the treatment of osteosarcoma (OS), satisfactory results are still difficult to achieve. Novel therapeutic modalities need to be developed for osteosarcoma treatment. The combined effects of tumor necrosis factor‐related apoptosis‐inducing ligand (...

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Published in:Journal of orthopaedic research 2010-06, Vol.28 (6), p.739-745
Main Authors: Hori, Takeshi, Kondo, Takashi, Kanamori, Masahiko, Tabuchi, Yoshiaki, Ogawa, Ryohei, Zhao, Qing-Li, Ahmed, Kanwal, Yasuda, Taketoshi, Seki, Shoji, Suzuki, Kayo, Kimura, Tomoatsu
Format: Article
Language:English
Subjects:
apoptosis
Apoptosis - drug effects
Bone Neoplasms - metabolism
Bone Neoplasms - pathology
Bone Neoplasms - radiotherapy
Cell Line, Tumor
Cell Survival - drug effects
Cell Survival - radiation effects
DR5
Gene Expression Regulation, Neoplastic - radiation effects
Humans
ionizing radiation
Osteosarcoma - metabolism
Osteosarcoma - pathology
Osteosarcoma - radiotherapy
Promoter Regions, Genetic
Receptors, TNF-Related Apoptosis-Inducing Ligand - genetics
Receptors, Tumor Necrosis Factor - genetics
RNA, Messenger - analysis
TNF-Related Apoptosis-Inducing Ligand - pharmacology
TRAIL
Up-Regulation
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Summary:Despite improvements in chemotherapy and surgery in the treatment of osteosarcoma (OS), satisfactory results are still difficult to achieve. Novel therapeutic modalities need to be developed for osteosarcoma treatment. The combined effects of tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and ionizing radiation (IR) on human OS cells were investigated. IR and TRAIL treatment synergistically decreased the cell viability and enhanced apoptosis in OS cell lines. IR pretreatment enhances TRAIL‐induced Bid and caspase‐3 activations. Decreases in the expression levels of the antiapoptotic proteins c‐FLIP and XIAP also associated with apoptosis enhancement. Furthermore, IR pretreatment enhanced DR4 and DR5 expressions at the transcription stage. These results can become the basic lines of evidence for the future treatment of OS using TRAIL with IR. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:739–745, 2010
ISSN:0736-0266
1554-527X
DOI:10.1002/jor.21056