微信公众号

官网二维码
中国癌症防治杂志

中国癌症防治杂志 ›› 2020, Vol. 12 ›› Issue (1): 33-38.doi: 10.3969/j.issn.1674-5671.2020.01.06

• 基础研究 • 上一篇    下一篇

MKP-1增强组蛋白去乙酰化酶抑制剂对脑胶质瘤干细胞敏感性及其作用机制

  

  1. 武汉市第三医院/武汉大学附属同仁医院  神经外科，120救治中心，胸外科
  • 出版日期:2020-02-25 发布日期:2020-03-10
  • 通讯作者: 罗才奎 E-mail：liuty8607@163.com
  • 基金资助:
    武汉市卫生计划生育委员会科研项目（WX17Q15）

MKP-1 enhancement of the sensitivity of histone deacetylase inhibitors to glioma stem cells and its underlying mechanism

  • Online:2020-02-25 Published:2020-03-10

PDF (PC)

238

赞

摘要： 目的 探讨MKP-1对组蛋白去乙酰化酶抑制剂（histone deacetylase inhibitors，HDACi）作用脑胶质瘤干细胞（glioma stem cells，GSC）敏感性的影响及可能的作用机制。方法 收集武汉市第三医院神经外科2016年1月至2018年12月收治的53例脑胶质瘤患者肿瘤及健康脑组织。RT-PCR检测MKP-1表达，分离并培养脑胶质瘤干细胞，采用MTT实验检测HDACi MS-275作用脑胶质瘤干细胞的IC50。以MKP-1过表达质粒转染干细胞构建差异表达MKP-1的脑胶质瘤干细胞模型，MTT实验分析HDACi MS-275的敏感性，CCK-8实验检测细胞增殖情况，RT-PCR及Western blot实验检测肿瘤干细胞相关因子SOX2、SOX9的表达，Western blot实验检测p38、JNK、ERK1/2的表达。结果 MKP-1在脑胶质瘤组织中的表达较健康脑组织明显降低（P<0.001）。HDACi MS-275作用GSC的IC50为（55.12±7.31） nmol/mL，作用后细胞增殖能力较对照组明显降低（P<0.001），MKP-1表达明显升高（P<0.001）。HDACi MS-275作用过表达MKP-1脑胶质瘤干细胞的IC50较对照组和空白组明显降低（P<0.001）。MKP-1组GSC增殖能力，SOX2、SOX9 mRNA和蛋白表达量均较对照组和空白组明显降低（P<0.001）。MKP-1组JNK和p38表达较均对照组和空白组降低（P<0.001），但ERK1/2表达差异无统计学意义（P＞0.05）。结论 脑胶质瘤干细胞对HDACi的敏感性与MKP-1表达有关，MKP-1可能通过调控SOX2、SOX9、p38、JNK而影响脑胶质瘤干细胞对HDACi的应答。

关键词: 脑胶质瘤, 干细胞, MKP-1, HDACi, p38, JNK

Abstract: Objective To investigate the effect of MKP-1 on the sensitivity of histone deacetylase inhibitors（HDACi） in glioma stem cells（GSC） and its underlying mechanism. Methods A total of 53 glioma patients  from  January  2016  to December  2018  in  the Department of Neurosurgery，Third Hospital of Wuhan，were enrolled to obtain the tumors and healthy brain tissues. MKP-1 expression was detected by RT-PCR. GSC were isolated and cultured. The IC50 of HDACi MS-275 on GSC was detected by MTT assay. MKP-1 overexpressing plasmid was used to transfect cells to construct a GSC model that differentially expresses MKP-1，and MTT assay was used to analyze its sensitivity to HDACi MS-275，CCK-8 assay was used to detect cell proliferation，RT-PCR and Western blot was used to detect the expression of GSC related factors SOX2 and SOX9，and Western blot was used to detect the expression of p38，JNK and ERK1/2. Results The expression of MKP-1 in glioma tissues was significantly lower than that in healthy brain tissues（P<0.001）. The IC50 of GSC treated with HDACi MS-275 was（55.12±7.31） nmol/mL，and the cell proliferation ability was significantly lower than that in the control group（P<0.001），and the expression of MKP-1 was significantly increased（P<0.001）. The IC50 of HDACi MS-275 on MKP-1 overexpressing GSC was significantly lower than that of the control group and blank group（P<0.001）. The proliferation ability，the mRNA，and protein expression of SOX2 and SOX9 of GSC in the MKP-1 group were significantly lower than those in the control group and blank group（P<0.001）. The expression of JNK and p38 in the MKP-1 group was lower than those in the control group and blank group（P<0.001），and there was no significant difference in ERK1/2 expression（P＞0.05）. Conclusion The sensitivity of HDACi on GSC is related to the expression of MKP-1. MKP-1 may regulate the reactivity of GSC to HDACi by regulating SOX2，SOX9，p38，and JNK.

Key words: Glioma, Stem cells, MKP-1, Histone deacetylase inhibitors, p38, JNK

中图分类号: 

  • R739.41