Inhibitory Effect of Decitabine-inhibeting Methylation of SHP-1 Gene on Proliferation and Apoptosis of MDS Cell Line Skm-1.
10.19746/j.cnki.issn.1009-2137.2019.05.030
- Author:
Ying HAN
1
;
Jin ZHANG
2
;
Jing JI
2
;
Yan-Bin PANG
2
;
Luo-Ming HUA
2
;
Zong-Hong SHAO
3
Author Information
1. Department of Hematology, Tianjin Medical University General Hospital, Tianjin 300052，China,Department of Hematology, The Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China.
2. Department of Hematology, The Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China.
3. Department of Hematology, Tianjin Medical University General Hospital, Tianjin 300052，China,E-mail:shaozonghong@sina.com.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
Cell Line;
Cell Line, Tumor;
Cell Proliferation;
Decitabine;
Humans;
Protein Tyrosine Phosphatase, Non-Receptor Type 6
- From:
Journal of Experimental Hematology
2019;27(5):1561-1567
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the phenotype and molecular mechanism of DCA on MDS cell model, and to study the response of chemotherapeutic medicines to MDS cells through multiple dimensions, such as cell proliferation, invasion, migration and apoptosis, thus revealing the molecular mechanism of DCA treatment of MDS and its relationship with SHP-1 gene methylation.
METHODS:MTT assay was used to determine the survival rate of MDS cells after treated by different concentrations of DCA. The effect of DCA on the invasion and migration of MDS cells was detected by Transwell assay method. Apoplexin V-FITCPI was used to detect apoptosis, the MDS treatment on the mechanism of DCA was investigated by Western blot and Real-time PCR experiment.
RESULTS:According to the experiment, it was found that tumor proliferation could be inhibited when MDS skm-1 cells was treated by DCA, and the absorbance was lower and the inhibitory effect was more obvious in the 2.0, 5.0 μmol/L DCA group than in the 0.5 μmol/L DCA group and the negative control group. Compared with the control group, the number of MDS skm-1 cells crossing through the transwell upper chamber was significantly decreased after DCA application. After treated with 0.5, 2.0 and 5.0 μmol/L DCA, the apoptosis rate of MDS cells was 4.54%, 9.31% and 16.58% respectively, while the apoptosis rate of the control group was 3.20%, which shows the apoptosis rate increased significantly with the concentration of DCA. After treatment of MDS cell lines with different concentration of DCA, the methylation status of SHP-1 gene was decreased with the increase of drug concentration, the expression of SHP-1 was increased, the expression of STAT3 was decreased and the level of phosphorylation was decreased.
CONCLUSION:By analyzing the phenotypic response of DCA treatment on MDS cells, it was found that interfere with MDS can be performed by inhibiting proliferation, metastasis, and inducing apoptosis in a dose-dependent way. It revealed that the molecular mechanism by DCA treatment can improve the methylation of SHP-1 gene and inhibit the expression of p-STAT3.
