Żwierełło Wojciech, Maruszewska Agnieszka, Skórka-Majewicz Marta, Wszołek Agata, Gutowska Izabela
Department of Medical Chemistry, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland.
Department of Physiology and Biochemistry, Institute of Biology, University of Szczecin, 70-453 Szczecin, Poland.
Int J Mol Sci. 2024 Nov 27;25(23):12773. doi: 10.3390/ijms252312773.
Glioblastoma remains one of the most treatment-resistant and malignant human cancers. Given the documented harmful effects of fluoride on the developing central nervous system and the rising incidence of brain tumors, especially among children, it is pertinent to explore the role of environmental toxins, including fluoride compounds, in the context of brain cancer. This study represents the first investigation into the influence of fluoride on mechanisms related to the invasiveness of human glioblastoma cells. We examined the effects of sodium fluoride (NaF) exposure on the migratory and invasive abilities of the U-87 human glioblastoma cell line, assessing levels of metalloproteinases MMP-2 and MMP-9 secreted by these cells. Additionally, the activation of metabolic pathways associated with invasiveness, including AKT and NF-κB, was analyzed. Our results suggest that the effects induced by NaF at physiologically high concentrations (0.1-10 µM) in U-87 glioblastoma cells may promote a pro-invasive phenotype.
胶质母细胞瘤仍然是最难治疗且最具恶性的人类癌症之一。鉴于已记录的氟化物对发育中的中枢神经系统的有害影响以及脑肿瘤发病率的上升,尤其是在儿童中,探讨包括氟化物化合物在内的环境毒素在脑癌背景下的作用是很有必要的。本研究首次调查了氟化物对人类胶质母细胞瘤细胞侵袭相关机制的影响。我们检测了氟化钠(NaF)暴露对U-87人类胶质母细胞瘤细胞系迁移和侵袭能力的影响,评估了这些细胞分泌的金属蛋白酶MMP-2和MMP-9的水平。此外,还分析了与侵袭相关的代谢途径(包括AKT和NF-κB)的激活情况。我们的结果表明,生理高浓度(0.1 - 10 µM)的NaF对U-87胶质母细胞瘤细胞诱导的影响可能会促进侵袭性表型。