阿来替尼抑制神经母细胞瘤SH-SY5Y细胞糖酵解  

Alectinib inhibits glycolysis of neuroblastoma cell line SH-SY5Y

作　　者：郭鹏[1] 马晓琳[1] GUO Peng;MA Xiao-lin(Department of Neurology,the Third People's Hospital of Ji-nan,Ji-nan SHANDONG 250132,China)

机构地区：[1]济南市第三人民医院神经内科

出　　处：《中国新药与临床杂志》2020年第1期53-56,共4页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的观察阿来替尼对神经母细胞瘤SH-SY5Y细胞糖酵解的作用。方法培养SH-SY5Y细胞分为对照组及1.25、2.5、5、10和20μmol·L^-1阿来替尼组,MTT法检测细胞增殖活性变化,流式细胞术检测细胞凋亡率,检测ALK表达正常和敲低的SH-SY5Y细胞乳酸产量变化;检测5μmol·L^-1阿来替尼对SH-SY5Y细胞糖酵解活性改变;Western blot法检测乳酸脱氢酶A(LDH-A)的表达。结果与对照组比较,1.25、2.5、5、10、20μmol·L^-1阿来替尼组SH-SY5Y细胞增殖率显著降低(P<0.05),细胞凋亡率显著增加(P <0.05);细胞内乳酸含量显著降低(P <0.05),且不依赖于ALK表达。5μmol·L^-1阿来替尼组SH-SY5Y细胞基础糖酵解活性值及最大糖酵解活性值相较于对照组显著下调(P <0.05)。与对照组相比,1.25、2.5、5和10μmol·L^-1阿来替尼组SH-SY5Y细胞LDH-A表达均显著下调(P <0.05)。结论阿来替尼抑制SH-SY5Y细胞增殖、诱导其凋亡,其机制可能与降低SH-SY5Y细胞糖酵解活性,抑制LDH-A表达有关。AIM To observe the effect of alectinib on the glycolysis of neuroblastoma SH-SY5Y cells. METHODS SH-SY5Y cells were treated with different concentrations of alectinib(0, 1.25, 2.5, 5, 10 and 20 μmol·L^-1) for 48 h. MTT assay and flow cytometry were used to detect cell proliferation activity and apoptosis rate, respectively. The changes of lactate production in SH-SY5Y cells and ALK-knockdown SH-SY5Y cells was determined. The glycolysis stress test kit were used to detect the glycolytic activity by 5 μmol·L-1 alectinib. Western blot assay was conducted to investigate the lactic dehydrogenase A(LDH-A) expression. RESULTS Compared with the control group(0 μmol·L-1 alectinib), the proliferation rate were significantly decreased, and the apoptosis rate were significantly increased in the alectinib(1.25, 2.5, 5,10, 20 μmol·L^-1) groups(P < 0.05). The intracellular lactate contents were significantly decreased in the alectinib groups(P < 0.05), which were not affected by ALK knockdown. The basic glycolysis activity and maximum glycolysis activity was significantly lower in the 5 μmol·L^-1 alectinib group than those in the control group(P < 0.05). The LDH-A expression were significantly downregulated in the alectinib(1.25, 2.5, 5, 10 μmol·L^-1) groups(P < 0.05). CONCLUSION Alectinib can inhibit the proliferation and induce the apoptosis of SH-SY5Y cells, which may be related to the reduction of the glycolytic activity and inhibition of the LDH-A expression.

关 键 词：阿来替尼 神经母细胞瘤 细胞凋亡 糖酵解 

分 类 号：R979.1[医药卫生—药品]