Effect of arsenic trioxide and 5-aza-2'-deoxycytidine on SHP-1, JAK3, TYK2 gene expression in K562 cells.
10.7534/j.issn.1009-2137.2014.02.011
- Author:
Xiao-Kun ZHANG
1
;
Jian-Min LUO
2
;
Jie SUN
3
Author Information
1. Department of Hematology, Xingtai people's Hospital of Hebei Medical University , Xingtai, 054000, Hebei Province, China. E-mail: farflybird@163.com.
2. Hebei Province Key Laboratory of Blood Disease, Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China.
3. Department of Hematology, Xingtai people's Hospital of Hebei Medical University , Xingtai, 054000, Hebei Province, China.
- Publication Type:Journal Article
- MeSH:
Arsenicals;
pharmacology;
Azacitidine;
administration & dosage;
analogs & derivatives;
pharmacology;
DNA Methylation;
Gene Expression Regulation, Leukemic;
drug effects;
Humans;
Janus Kinase 3;
metabolism;
K562 Cells;
Oxides;
pharmacology;
Protein Tyrosine Phosphatase, Non-Receptor Type 6;
metabolism;
TYK2 Kinase;
metabolism
- From:
Journal of Experimental Hematology
2014;22(2):323-328
- CountryChina
- Language:Chinese
-
Abstract:
This study was purposed to explore the effects of a methylation inhibitor arsenic trioxide (As2O3, ATO) and 5-Aza-2'-deoxycytidine (5-aza-CdR) on the expression of JAK-STAT signal transduction pathway in family members JAK3, TYK2 and hematopoietic cell phosphatase SHP-1 in chronic myeloid leukemia cell line K562 and their roles in pathogenesis of leukemia. The K562 cells were divided into 3 groups:single drug-treated group, combined 2 drugs-treated group, group without drug treatment as control. The concentration of 5-aza-CdR were 0.5, 1, 2 µmol/L; the concentration of ATO was 1, 2.5, 5 µmol/L; the concentration of combined drugs was ATO 1 µmol/L + 5-aza-CdR 0.5 µmol/L, ATO 2.5 µmol/L + 5-aza-CdR 1 µmol/L, and ATO 5 µmol/L + 5-aza-CdR 2 µmol/L. The K562 cells were treated with above-mentioned concentration of drugs for 24, 48 and 72 hours, then the total RNA of cells was extracted, the JAK3, TYK2 and SHP-1 expressions were detected by real-time quantitative-PCR. The results showed that after the K562 cells were treated with ATO and 5-aza-CdR alone and their combination, the expression of SHP-1 mRNA increased, the expressions of JAK3 mRNA and TYK2 mRNA decreased along with increasing of concentration and prolonging of time, displaying the concentration and time-dependency. The SHP-1 negatively related with JAK3 and TYK2. The effect of SHP-1 on JAK3 was significantly higher than that on TYK2. It is concluded that when the K562 cells are treated with ATO and 5-aza-CdR alone and their combination, the expression of SHP-1 is up-regulated and the expressions of JAK3, TYK2 are down-regulated in concentration-and time-dependent manners, moreover the ATO and 5-aza-CdR show synergies demethylation effect. The SHP-1 gene exert effect possibly through inhibiting the JAK/STAT pathway, the JAK3 is affected more than TYK2, the JAK3 may exert more important role in TAK/STAT pathway.
