双酚S通过诱导神经胶质瘤细胞干性维持增强替莫唑胺抵抗的机制探讨

Exploration of the mechanism by which bisphenol S enhances temozolomide resistance by inducing stemness maintenance in glioma cells

目的探讨双酚S(BPS)在神经胶质瘤细胞干性维持中的作用,及其与替莫唑胺(TMZ)抵抗的关系。方法以BPS刺激神经胶质瘤U251细胞,必要时以TMZ处理细胞,细胞成球实验检测细胞成球能力;平板克隆实验观察细胞克隆形成能力;MTT实验观察细胞存活能力;蛋白印迹和/或免疫荧光实验检测细胞CD133和SOX-2蛋白表达。结果与对照组(Control组)相比,BPS(0.1、1、10μM)处理后,U251细胞干细胞球直径明显增加,干细胞球数量也显著增加(P<0.05)。BPS(0.1、1、10μM)处理明显增强U251细胞克隆形成能力(P<0.01)。BPS(10μM)显著上调U251细胞CD44和CD133蛋白表达(P<0.01)。BPS(10μM)处理显著抵抗TMZ诱导的细胞活力降低(P<0.05)。结论BPS在神经胶质瘤细胞干性维持中发挥作用,该作用可能与TMZ抵抗有关。

Objective To investigate the role of bisphenol S(BPS)in the stemness maintenance of glioma cells and the relationship with temozolomide(TMZ)resistance.Methods Glioma U251 cells were stimulated with BPS and treated with TMZ if necessary,and the cell sphere-forming ability was detected by cell sphere-forming assay.Colony formation assay was performed to observe the clone formation ability of cells.MTT assay was performed to observe cell viability.Western blot or/and immunofluorescence assay was performed to detect the cellular CD133 and SOX-2 protein expression.Results The diameter and the number of stem cell spheres of U251 cells were significantly increased by BPS(0.1μM,1μM,10μM)treatment compared to control group(P<0.01).BPS(0.1μM,1μM,10μM)treatment significantly enhanced the clone formation ability of U251 cells(P<0.01).BPS(10μM)significantly upregulated CD44 and CD133 protein expression in U251 cells(P<0.01).BPS(10μM)treatment significantly resisted TMZ-induced decrease in cell viability(P<0.01).Conclusion BPS plays a role in the maintenance of cell stemness in glioma cells,which may be related to TMZ resistance.