Metformin Radiosensitizing Effect on Hypoxic Oral Squamous Cell Carcinoma Cells by GAPDH and TAGLN2.
Autor: | Santos EM; Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil., Farias LC; Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil., Guimarães TA; Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil., Santos EMS; Institute of Education, Science and Technology, Instituto Federal Do Norte de Minas Gerais, Araçuaí, Brazil., de Jesus SF; Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil., de Souza MG; Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil., de Souza PC; Dilson Godinho Hospital, Montes Claros, Minas Gerais, Brazil., Santiago L; Dilson Godinho Hospital, Montes Claros, Minas Gerais, Brazil., D'Angelo MFSV; Department of Computer Science, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil., De-Paula AMB; Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil., Santos SHS; Institute of Agricultural Sciences (ICA), Food Engineering, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil., Guimarães ALS; Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil.; Dilson Godinho Hospital, Montes Claros, Minas Gerais, Brazil. |
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Jazyk: | angličtina |
Zdroj: | Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology [J Oral Pathol Med] 2024 Oct; Vol. 53 (9), pp. 567-576. Date of Electronic Publication: 2024 Aug 19. |
DOI: | 10.1111/jop.13576 |
Abstrakt: | Objective: Tumor hypoxia is associated with a poorer prognosis in cancer patients and can diminish the efficacy of radiation therapy (RT). This study investigates the potential of metformin to enhance radiosensitivity in hypoxic cancer cells. Methods: Preliminary experiments were conducted to validate the impact of hypoxia on radiation response. Reactive oxygen species (ROS) levels, cell migration, and cell death were assessed in hypoxic, radiated cells treated with metformin. Proteomic and ontological analyses were employed to identify molecular targets associated with the radiosensitizing effect of metformin. Proteomic and ontological findings were validated through patient samples and in vitro studies. Results: Metformin amplified cell death, induced DNA fragmentation, decreased cell migration, and elevated ROS levels in hypoxic, radiated cells. Proteomic analyses revealed that GAPDH and TAGLN2 were identified as pivotal targets linked to the radiosensitizing effect of metformin. Oral cancer patients exhibited elevated levels of TAGLN2 and reduced levels of GAPDH. Metformin downregulated TAGLN2 and upregulated GAPDH in hypoxic, radiated cells. Additionally, metformin reduced levels of mutated p53. Conclusions: This study suggests that metformin can enhance radiosensitivity in hypoxic cells, operating through modulation of GAPDH and TAGLN2. Furthermore, metformin effectively reduces mutated p53 levels in radiated cells under hypoxic conditions. (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.) |
Databáze: | MEDLINE |
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