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

✍ Scribed by Takeshi Hori; Takashi Kondo; Masahiko Kanamori; Yoshiaki Tabuchi; Ryohei Ogawa; Qing-Li Zhao; Kanwal Ahmed; Taketoshi Yasuda; Shoji Seki; Kayo Suzuki; Tomoatsu Kimura

• Publisher: Elsevier Science
• Year: 2009
• Tongue: English
• Weight: 228 KB
• Volume: 28
• Category: Article
• ISSN: 0736-0266
• DOI: 10.1002/jor.21056

✦ Synopsis

Abstract

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