美金刚诱导恶性胶质瘤细胞中NMDAR1介导的自噬性细胞死亡。
Memantine Induces NMDAR1-Mediated Autophagic Cell Death in Malignant Glioma Cells.
作者信息
Yoon Wan-Soo, Yeom Mi-Young, Kang Eun-Sun, Chung Yong-An, Chung Dong-Sup, Jeun Sin-Soo
机构信息
Department of Neurosurgery, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea.
Clinical Research Laboratory, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea.
出版信息
J Korean Neurosurg Soc. 2017 Mar;60(2):130-137. doi: 10.3340/jkns.2016.0101.006. Epub 2017 Mar 1.
OBJECTIVE
Autophagy is one of the key responses of cells to programmed cell death. Memantine, an approved anti-dementia drug, has an antiproliferative effect on cancer cells but the mechanism is poorly understood. The aim of the present study was to test the possibility of induction of autophagic cell death by memantine in glioma cell lines.
METHODS
Glioma cell lines (T-98 G and U-251 MG) were used for this study.
RESULTS
The antiproliferative effect of memantine was shown on T-98 G cells, which expressed N-methyl-D-aspartate 1 receptor (NMDAR1). Memantine increased the autophagic-related proteins as the conversion ratio of light chain protein 3-II (LC3-II)-/LC3-I and the expression of beclin-1. Memantine also increased formation of autophagic vacuoles observed under a transmission electron microscope. Transfection of small interfering RNA (siRNA) to knock down NMDAR1 in the glioma cells induced resistance to memantine and decreased the LC3-II/LC3-I ratio in T-98 G cells.
CONCLUSION
Our study demonstrates that in glioma cells, memantine inhibits proliferation and induces autophagy mediated by NMDAR1.
目的
自噬是细胞对程序性细胞死亡的关键反应之一。美金刚是一种已获批的抗痴呆药物，对癌细胞具有抗增殖作用，但其机制尚不清楚。本研究的目的是测试美金刚在胶质瘤细胞系中诱导自噬性细胞死亡的可能性。
方法
本研究使用了胶质瘤细胞系（T-98 G和U-251 MG）。
结果
美金刚对表达N-甲基-D-天冬氨酸1型受体（NMDAR1）的T-98 G细胞显示出抗增殖作用。美金刚增加了自噬相关蛋白，如轻链蛋白3-II（LC3-II）与LC3-I的转化率以及beclin-1的表达。美金刚还增加了透射电子显微镜下观察到的自噬泡的形成。在胶质瘤细胞中转染小干扰RNA（siRNA）以敲低NMDAR1可诱导对美金刚的抗性，并降低T-98 G细胞中的LC3-II/LC3-I比率。
结论
我们的研究表明，在胶质瘤细胞中，美金刚抑制增殖并诱导由NMDAR1介导的自噬。
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