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中华神经创伤外科电子杂志

中华神经创伤外科电子杂志 ›› 2021, Vol. 07 ›› Issue (05) : 261 -265. doi: 10.3877/cma.j.issn.2095-9141.2021.05.002

基础研究

NHE1抑制剂改善胶质母细胞瘤细胞对替莫唑胺耐药性的研究
孙明阳1, 刘艳坤2, 陈思1, 李玉凤2, 李玉辉1,†()   
  1. 1. 063001　唐山市人民医院神经外科
    2. 063001　唐山市人民医院肿瘤研究所
  • 收稿日期:2021-06-03 出版日期:2021-10-15
  • 通信作者: 李玉辉
  • 基金资助:
    唐山市科技创新团队培养计划项目基金(18130203B); 河北省分子肿瘤学重点实验室(SZX2020042)

NHE1 inhibitor improves temozolomide-resistance of human glioblastoma cells

Mingyang Sun1, Yankun Liu2, Si Chen1, Yufeng Li2, Yuhui Li1,†()   

  1. 1. Department of Neurosurgery, Tangshan People’s Hospital, Tangshan 063001, China
    2. Cancer Institute, Tangshan People’s Hospital, Tangshan 063001, China
  • Received:2021-06-03 Published:2021-10-15
  • Corresponding author: Yuhui Li
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引用本文：

孙明阳, 刘艳坤, 陈思, 李玉凤, 李玉辉. NHE1抑制剂改善胶质母细胞瘤细胞对替莫唑胺耐药性的研究[J/OL]. 中华神经创伤外科电子杂志, 2021, 07(05): 261-265.

Mingyang Sun, Yankun Liu, Si Chen, Yufeng Li, Yuhui Li. NHE1 inhibitor improves temozolomide-resistance of human glioblastoma cells[J/OL]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2021, 07(05): 261-265.

目的

分析Na+/H+交换蛋白1（NHE1）抑制剂Cariporide改善对替莫唑胺（TMZ）耐药的胶质母细胞瘤（GBM）细胞耐药性的作用。

方法

采用本课题组前期建立的对TMZ耐药（TR）细胞系U87/TR和U251/TR，Cariporide分别处理各组细胞，乙酰甲酯化的2’，7’-双(2-羧乙基)-5(6)-羧荧光素荧光探针分析NHE1的活性，CCK-8法检测细胞增殖活性，计算细胞存活率。

结果

CCK-8法证实U87/TR和U251/TR对TMZ耐药。U87/TR和U251/TR细胞内NHE1活性、细胞存活率均分别显著高于亲本U87和U251细胞，差异均具有统计学意义（P<0.05）；Cariporide处理的U87/TR和U251/TR细胞内NHE1活性显著高于亲本U87和U251细胞，但分别显著低于未添加Cariporide的U87/TR和U251/TR细胞，差异均具有统计学意义（P<0.05）；在325 μmol/L TMZ培养的条件下，Cariporide处理的U87/TR和U251/TR细胞存活率显著高于亲本U87和U251细胞，但分别显著低于未添加Cariporide的U87/TR和U251/TR细胞，差异均具有统计学意义（P<0.05）。

结论

采用Cariporide阻断NHE1活性可部分改善GBM细胞对TMZ的耐药性。

关键词: 胶质母细胞瘤, 替莫唑胺, 耐药, NHE1抑制剂
Objective

To analyze the effect of Na+/H+ exchanger 1 (NHE1) inhibitor Cariporide on improving temozolomide (TMZ)-resistance of human glioblastoma (GBM) cells.

Methods

Each group of cells was treated with TMZ resistant (TR) cell lines U87/TR and U251/TR, Cariporide which established in the early stage of this research group. The NHE1 activity was detected with acetoxymethyl ester of 2’,7’-Bis(2-carboxyethyl)-5(6)-carboxyfluorescein fluorescent probe. The cell viability was analyzed by CCK-8 and the cell survival rate was calculated.

Results

The TMZ-resistances of U87/TR and U251/TR were confirmed by CCK-8 method. The NHE1 activity and cell survival rate of U87/TR and U251/TR were significantly higher than those of parental U87 and U251 cells, respectively (P<0.05). The NHE1 activities of Cariporide-treated U87/TR and U251/TR cells were still significantly higher than their parental cells, they were significantly lower than U87/TR and U251/TR cells without Cariporide, respectively (P<0.05). Under the conditions cultured at 325 μmol/L TMZ, the cell survival rate of Cariporide-treated U87/TR and U251/TR cells remained significantly higher than their parental cells, they were significantly lower than U87/TR and U251/TR cells without Cariporide, respectively (P<0.05).

Conclusion

Inhibition of NHE1 activity with Cariporide could partially improve the TMZ-resistance of GBM cells.

Key words: Glioblastoma, Temozolomide, Drug resistance, NHE1 inhibitor
图1 CCK-8分析各组细胞在325 μmol/L TMZ中的存活率
图2 BCECF-AM荧光探针分析各组细胞内FIR值
图3 CCK-8分析各组细胞在325 μmol/L TMZ中的细胞存活率
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