Effect of arsenic trioxide and 5-aza-2'-deoxycytidine on SHP-1, JAK3, TYK2 gene expression in K562 cells / 中国实验血液学杂志
Journal of Experimental Hematology
; (6): 323-328, 2014.
Article
de Zh
| WPRIM
| ID: wpr-349714
Bibliothèque responsable:
WPRO
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.
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Oxydes
/
Pharmacologie
/
Composés de l'arsenic
/
Azacitidine
/
Régulation de l'expression des gènes dans la leucémie
/
Méthylation de l'ADN
/
Cellules K562
/
Protein Tyrosine Phosphatase, Non-Receptor Type 6
/
Janus kinase 3
/
TYK2 Kinase
Limites du sujet:
Humans
langue:
Zh
Texte intégral:
Journal of Experimental Hematology
Année:
2014
Type:
Article