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