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 (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.
Hori
Takeshi
T
Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama-city, Toyama, Japan.
Kondo
Takashi
T
Kanamori
Masahiko
M
Tabuchi
Yoshiaki
Y
Ogawa
Ryohei
R
Zhao
Qing-Li
QL
Ahmed
Kanwal
K
Yasuda
Taketoshi
T
Seki
Shoji
S
Suzuki
Kayo
K
Kimura
Tomoatsu
T
D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D015854:Up-Regulation
D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human