메트포르민과 방사선치료 복합요법에 의한 두경부암의 증식 억제
Synergistic Inhibition of Head and Neck Cancer Cell Proliferation by Combined Metformin and Radiotherapy Treatment
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Background and Objectives Metformin, a commonly used antidiabetic drug, has been reportedto exhibit promising anticancer effects across various tumor types. This study investigatedthe effectiveness of combining metformin with radiotherapy (RT) to treat head and necksquamous cell carcinoma (HNSCC). Materials and Method In vitro experiments were conducted in which FaDu and SCC-25cells were treated with metformin, followed by irradiation. Cell proliferation was evaluated byMTT assay, and apoptosis was assessed by staining with annexin V-fluorescein isothiocyanate/propidium iodide, followed by flow cytometry. Western blotting was performed to evaluatechanges in apoptotic markers. In vivo experiments were performed using a murine AT-84allograft model, where tumor volume was measured and serum samples were collected to assessthe level of vascular endothelial growth factor (VEGF). Results The combination of metformin and RT significantly reduced cell proliferation in adose- and time-dependent manner, and led to a significant increase in the apoptotic rate, accompaniedby the upregulation of cleaved caspase-8 and FoxO3, and the downregulation ofBcl-2. The combination treatment also exhibited antiangiogenic effects, as shown by the reducedhypoxia-inducible factor-1 alpha level and inhibited tube formation in the endothelialcells. The combined therapy in the mouse model led to marked decrease in tumor volume andthe serum VEGF level in comparison to both the control group and the RT alone. Conclusion The concurrent use of metformin and RT successfully suppressed cell proliferation,triggered apoptosis, and increased the antiangiogenic effects in HNSCC. These resultssupport the use of metformin as an adjunct to RT for the treatment of HNSCC.
Abstract
Background and Objectives Metformin, a commonly used antidiabetic drug, has been reportedto exhibit promising anticancer effects across various tumor types. This study investigatedthe effectiveness of combining metformin with radiotherapy (RT) to treat head and necksquamous cell carcinoma (HNSCC). Materials and Method In vitro experiments were conducted in which FaDu and SCC-25cells were treated with metformin, followed by irradiation. Cell proliferation was evaluated byMTT assay, and apoptosis was assessed by staining with annexin V-fluorescein isothiocyanate/propidium iodide, followed by flow cytometry. Western blotting was performed to evaluatechanges in apoptotic markers. In vivo experiments were performed using a murine AT-84allograft model, where tumor volume was measured and serum samples were collected to assessthe level of vascular endothelial growth factor (VEGF). Results The combination of metformin and RT significantly reduced cell proliferation in adose- and time-dependent manner, and led to a significant increase in the apoptotic rate, accompaniedby the upregulation of cleaved caspase-8 and FoxO3, and the downregulation ofBcl-2. The combination treatment also exhibited antiangiogenic effects, as shown by the reducedhypoxia-inducible factor-1 alpha level and inhibited tube formation in the endothelialcells. The combined therapy in the mouse model led to marked decrease in tumor volume andthe serum VEGF level in comparison to both the control group and the RT alone. Conclusion The concurrent use of metformin and RT successfully suppressed cell proliferation,triggered apoptosis, and increased the antiangiogenic effects in HNSCC. These resultssupport the use of metformin as an adjunct to RT for the treatment of HNSCC.
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