去甲斑蝥素通过丝裂原活化蛋白激酶／细胞外信号调节蛋白激酶信号通路对胶质瘤U87细胞增殖及凋亡的影响  

Effects of norcantharidin on proliferation and apoptosis of glioma cells via mitogen - activated pro-tein kinase/extracellular regulated protein kinase signaling pathway

作　　者：庞长河[1] 薛亚轲[1] 董阳[1] 王晓涛[1] 魏新亭[1] Pang Changhe;Xue Yake;Dong ）rang;Wang Xiaotao;Wei Xinting(Department of Neurosurgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Chin)

机构地区：[1]郑州大学第一附属医院神经外科,450052

出　　处：《中华实验外科杂志》2018年第6期1080-1082,共3页Chinese Journal of Experimental Surgery

基　　金：河南省医学科技攻关项目（201702033）

摘　　要：目的观察去甲斑蝥素（NCTD）对胶质瘤细胞增殖及凋亡的影响。方法体外培养胶质瘤U87细胞，不同浓度NCTD（25、50、100、200 μmol/L）分别处理细胞24、48 h，噻唑蓝（MTT）法检测NCTD对U87细胞的增殖抑制作用；流式细胞仪测定细胞凋亡；Western blot检测丝裂原活化蛋白激酶/细胞外信号调节蛋白激酶信号通路（MAPK/ERK）信号通路的表达。结果NCTD对U87细胞有明显生长抑制作用，在一定程度上呈剂量时间依赖性，NCTD作用24、48 h后半数抑制浓度（IC50）分别为147.7、62.5 μmol/L，对细胞增殖具有明显抑制作用（F＝30.234、42.106，P＝0.000）；30、50 μmol/L NCTD作用U87细胞10 h，细胞凋亡率分别为（6.8±1.2）%、（17.2±2.0）%，较未处理对照组（1.2±0.9）%比较，差异有统计学意义（F＝405.761，P＝0.000）；NCTD可明显下调细胞MEK和ERK蛋白的磷酸化水平，差异有统计学意义（P＝0.007）。结论NCTD可以通过抑制U87细胞MAPK/ERK信号传导通路的方式抑制细胞增殖并促进凋亡。Objective To investigate the effects of norcantharidin （NCTD） on the proliferation and apoptosis on glioma cells.Methods Glioma U87 cells were treated with various concentrations of NCTD （25, 50, 100, 200 μmol/L） for 24, 48 h. The effects of NCTD on the proliferation and apoptosis of glioma cells were measured by methyl thiazol tetrazolium （MTT） assay and flow cytometry. The Mitogen-activated protein kinase/extracellular regulated protein kinase （MAPK/ERK） signaling pathway changes were detected by Western blotting.Results The results showed that NCTD effectively inhibited cell growth and induced apoptosis in U87 cells in a time- and dose-dependent manner. After incubation with NCTD for 24 h and 48 h, the average half maximal inhibitory concentration （IC50） was 147.7 μmol/L and 62.5 μmol/L, respectively. It could significantly inhibit proliferation at 24 h and 48 h （F=30.234, 42.106, P=0.000）. As compared with the control group [（1.2±0.9）%], the cell apoptosis rate induced by 30, 50 μmol/L of NCTD for 10 h was （6.8±1.2）% and （17.2±2.0）%, respectively, which indicated that NCTD could induce apoptosis of cells in a dose-dependent manner （F=405.761, P=0.000）. Western blotting results revealed that the phospho-MEK and phospho-ERK were down-regulated significantly in NCTD group as compared with control group （P=0.007）.Conclusion Our findings demonstrated that NCTD inhibited proliferation and induced apoptosis of U87 glioma cells through MAPK/ERK signaling pathway.

关 键 词：胶质瘤 去甲斑蝥素 丝裂原活化蛋白激酶/细胞外信号调节蛋白激酶信号通路 脱噬作用 

分 类 号：R96[医药卫生—药理学]