[Effect of arsenic trioxide and 5-aza-2'-deoxycytidine on SHP-1, JAK3, TYK2 gene expression in K562 cells].

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.

• Authors: Xiao-Kun Zhang, Jian-Min Luo, Jie Sun
• Journal: Zhongguo shi yan xue ye xue za zhi (Zhongguo Shi Yan Xue Ye Xue Za Zhi) Vol. 22 Issue 2 Pg. 323-8 (Apr 2014) ISSN: 1009-2137 [Print] China
• PMID: 24762999 (Publication Type: Journal Article)

Chemical References

• Arsenicals
• Oxides
• Decitabine
• JAK3 protein, human
• Janus Kinase 3
• TYK2 Kinase
• TYK2 protein, human
• PTPN6 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 6
• Azacitidine
• Arsenic Trioxide

Topics

• Arsenic Trioxide
• Arsenicals (pharmacology)
• Azacitidine (administration & dosage, analogs & derivatives, pharmacology)
• DNA Methylation
• Decitabine
• 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)