title: Synergistic effect of celecoxib in tumor necrosis factor‑related apoptosis‑inducing ligand treatment in osteosarcoma cells.
abstract: Tumor necrosis factor-related apoptosis‑inducing ligand (TRAIL) is under clinical development as a cancer therapeutic as it has been shown to induce apoptosis in numerous types of cancer cells without significant toxicity towards normal cells. However, the majority of osteosarcoma (OS) tumors are resistant to TRAIL. Thus, the development of cancer therapeutics that overcome TRAIL resistance is required. In the present study, celecoxib (CXB), a non-steroidal anti‑inflammatory drug, was administered in combination with TRAIL to induce cell apoptosis and the doses of the two drugs were simultaneously reduced. The effects of this combination treatment were examined in MG-63 human OS cancer cell lines in culture. Assays of proliferation, apoptosis and tumor growth were performed, along with analysis of the proteins involved. The results revealed that CXB sensitized TRAIL-resistant MG-63 OS cells to TRAIL‑induced apoptosis through downregulation of cellular B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, caspase-8 and caspase-3. Furthermore, combination treatment reduced tumor growth in a nude rat model. In conclusion, the experimental results provided evidence that the combined administration of CXB and TRAIL is potentially a novel treatment method of OS tumors.
authors: Department of Orthopaedics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Gong
authors: G
authors: Liu
authors: Department of Orthopaedics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Ming-Yang
authors: MY
authors: Yu
authors: Department of Orthopaedics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Xu
authors: X
authors: Huang
authors: Department of Orthopaedics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Dong
authors: D
authors: Zhu
authors: Department of Orthopaedics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Shihuan
authors: S
authors: Cheng
authors: Department of Orthopaedics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Renshi
authors: R
authors: Ma
authors: Department of Orthopaedics, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors: Guishan
authors: G
authors: Gu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011720:Pyrazoles / Q000627:therapeutic use / Q000633:toxicity*; D051381:Rats; D013449:Sulfonamides / Q000627:therapeutic use / Q000633:toxicity*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000627:therapeutic use / Q000633:toxicity*; D014183:Transplantation, Heterologous; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019253:Proto-Oncogene Proteins c-bcl-2; D011720:Pyrazoles; D013449:Sulfonamides; D053221:TNF-Related Apoptosis-Inducing Ligand; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053181:Caspase 8; D000068579:Celecoxib