Background/Aim: Sorafenib, an oral multi-kinase inhibitor, has been shown to improve the outcome of patients with osteosarcoma (OS). However, the anti-OS effect and mechanism of sorafenib has not yet been fully understood. The main purpose of this study was to investigate the effect of sorafenib on apoptotic signaling and Nuclear Factor-ĸB (NF-ĸB)-mediated anti-apoptotic and metastatic potential in OS in vitro. Materials and Methods: The effect of sorafenib on apoptotic signaling transduction, anti-apoptotic, and metastatic potential of OS U-2 cells was verified with flow cytometry, trans-well invasion/migration, and western blotting assay.
Results: Sorafenib induced the extrinsic and intrinsic apoptotic pathways. In addition, sorafenib reduced the invasion and migration ability of OS cells, induced NF-ĸB activation, and the expression of anti-apoptotic proteins and metastasisassociated proteins encoded by NF-ĸB target genes. Conclusion: Sorafenib led to stimulation of extrinsic/intrinsic apoptotic pathways and NF-ĸB inactivation in U-2 OS cells.Osteosarcoma (OS) is the common form of malignant bone tumor that frequently occurs in children and young adults (1). Conventional treatment strategies for osteosarcoma usually consist of surgery, chemotherapy, and radiotherapy, but the anti-OS efficacy of conventional treatment strategies is limited by chemo-radioresistance and metastasis (2, 3). Nuclear factor-ĸB (NF-ĸB), an oncogenic transcription factor, mediates chemo-radioresistance and metastasis by modulating the expression of anti-apoptotic and invasion-associated proteins encoded by NF-ĸB target oncogenes (4, 5). Suppression of NF-ĸB activation not only increases chemo-radiosensitivity but also reduces the metastatic potential of OS cells (6-9).In addition to improving chemo-radio resistance, how to effectively elicit cell death is also crucial for the treatment of OS. Apoptosis, a form of programmed cell death, is initiated by extrinsic (death receptor) and intrinsic (mitochondrial) signaling pathways, and is carried out by caspases (10). Treatment of OS cells and animal models with anticancer agents leads to 1251 *These Authors contributed equally to this study.
A simple and facile strategy using the all or none formation of dsDNA-templated copper nanoclusters on specific-primer PCR fragments was designed to fluorescently identify the T315I single nucleotide variant on the BCR–ABL1 gene.
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