β-羟丁酸对脑胶质瘤细胞增生糖酵解的影响

Effects of β-hydroxybutyrate on the proliferation and glycolysis in glioma cells

目的本研究探讨生酮饮食(ketogenic diet,KD)代谢产物之一的β-羟丁酸(β-hydroxybutyrate,β-HB)对脑胶质瘤细胞增生及糖酵解水平的影响,研究KD治疗脑胶质瘤的机制。方法用不同浓度的β-HB处理脑胶质瘤细胞系U87及LN229后,通过CCK8实验检测细胞增生,糖酵解压力测试检测细胞糖酵解能力,实时定量聚合酶链式反应(real-time quantitative polymerase chain reaction,RT-qPCR)法检测c-myc基因表达,Western blotting法检测c-myc蛋白表达。结果β-HB对LN229及U87细胞的生长抑制随着药物浓度增加而升高,呈现出剂量依赖性;与未处理组相比,实验组细胞糖酵解水平及最大糖酵解能力明显降低;经过β-HB处理后细胞c-myc表达降低。结论β-HB可能通过c-myc抑制脑胶质瘤细胞U87及LN229的糖酵解能力,从而影响细胞增生。提示KD可以作为治疗脑胶质瘤的方法之一。

Objective To investigate the effects ofβ-hydroxybutyrate(β-HB),one of the ketogenic diet(KD)metabolites,on the proliferation and glycolysis of glioma cell lines to reveal the mechanisms of KD in the treatment of glioma.Methods After treated with different concentrations ofβ-HB,the proliferation of glioma cell lines U87 and LN229 was detected with CCK8 assay and glycolysis ability of cells was measured with glycolysis stress test.Further,the transcription factor c-myc expression was detected with Western blotting and realtime quantitative polymerase chain reaction(RT-qPCR).Resultsβ-HB can inhibit the proliferation of glioma cells in a dose-dependent manner.Compared with the untreated group,the glycolysis level and maximum glycolytic capacity was decreased and the expression of c-myc was down-regulated in the experimental groups.Conclusionβ-HB can affect the glycolytic capacity of glioma cell lines U87 and LN229 through c-myc,and thus inhibit cell growth.It is suggested that KD can be used as an efficacious therapy agent for glioma.