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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
Author(s) -
Hori Takeshi,
Kondo Takashi,
Kanamori Masahiko,
Tabuchi Yoshiaki,
Ogawa Ryohei,
Zhao QingLi,
Ahmed Kanwal,
Yasuda Taketoshi,
Seki Shoji,
Suzuki Kayo,
Kimura Tomoatsu
Publication year - 2010
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21056
Subject(s) - apoptosis , xiap , osteosarcoma , tumor necrosis factor alpha , cancer research , programmed cell death , ionizing radiation , necrosis , receptor , chemistry , biology , caspase , medicine , immunology , pathology , biochemistry , irradiation , physics , nuclear physics
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