Effects of arsenic trioxide on intracelluar SOCS-1 gene methylation and P-STAT3 expression in multiple myeloma cells
10.3760/cma.j.issn.1673-422X.2012.08.021
- VernacularTitle:三氧化二砷诱导骨髓瘤细胞SOCS-1基因去甲基化及其对P-STAT3蛋白表达的影响
- Author:
Mingming WANG
;
Junpei HU
;
Lifang ZOU
;
Hongju DOU
;
Yiyun YAO
;
Qi ZHU
- Publication Type:Journal Article
- Keywords:
Multiple myeloma;
Methylation;
Apoptosis;
Arsenic trioxide;
SOCS-1 gene
- From:
Journal of International Oncology
2012;39(8):633-636
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of arsenic trioxide (AS2O3)on SOCS-1 gene methylation and expression of P-STAT3 in multiple myeloma (MM) cells.Methods MM cell lines U266 and CZ-1 were used as in vitro models.Methylation status of SOCS-1 gene was detected by the methylation specific PCR (MSP)while P-STAT3 protein expression was determined by Western blotting assay before and after AS2O3 treatment.Meanwhile growth inhibition and apoptosis of MM cells were determined by flow cytometry.Results Hypermethylation of SOCS-1 gene was observed in each MM cell line compared with wide type.After exposure to AS2O3,it was shown that SOCS-1 gene was demethylated obviously,meanwhile the expression level of P-STAT3 protein and cell proliferation was inhibited significantly in each cell line.The apoptosis rate was increased.When U266 and CZ-1 were treated with AS2O3 of 0,0.5,1.0,2.0 μmol/L respectively,the total cell apoptosisis ratio of U266 was 0.06％,0.56％,48.96％,61.07％ (X2 =9.19,P ＜ 0.05); and the total cell apoptosisis ratio of CZ-1 was 4.2％,,40.3％,,47.72％,,68.49％ (X2 =8.96,P ＜0.05 ).Conclusion AS2O3 could inhibit JAK/STAT signal transduction pathway by inducing SOCS-1 gene demethylation in MM cells which might be related to cell apoptosis.
