The Effect of Decitabine Combined with Arsenic Trioxide on DAPK Gene and HL-60 Cell Proliferation and Apoptosis

Jinhai Ren,Jingjing Yao,Xiaoling Guo,Xiaonan Guo,Shengxin Cai

doi:10.4236/jct.2015.615134

Abstract

Purpose: Our study was to detect the effect of Decitabine (DAC) combined with arsenic trioxide (AS2O3) on DAPK gene and HL-60 cell proliferation and apoptosis. Methods: DAC and AS2O3 monotherapy, combination treatment and DAC pretreatment were used in this study after incubating with HL-60 cell for 24 h, 48 h, 72 h. CCK8 was used to detect the cell proliferation of HL-60 cell. Flow cytometry was used to detect the cell apoptosis. Then, we used RT-PCR to obtain the gene expression level of DAPK. Results: HL-60 cells were treated with different concentrations of DAC (20 μmol/L, 40 μmol/L, 80 μmol/L), AS2O3 (1 μmol/L, 2.5 μmol/L, 5 μmol/L) monotherapy for 24 h, 48 h, 72 h; along with the extension of the drug concentration and time, proliferation inhibition rate had gradually increased. Monotherapy of DAC, AS2O3 could inhibit the proliferation and induce apoptosis of HL-60 cells, and was time- and dose-dependent. DAC (80 μmol/L) was firstly used for pretreatment, and then, different concentrations of AS2O3 (1 μmol/L, 2.5 μmol/L, 5 μmol/L) were used for 24 h, 48 h, 72 h. It was found that cell proliferation inhibition rate and apoptosis rate had increased significantly. When the two drugs were used together, the increasing proliferation inhibition rate, apoptosis rate and DAPK had become more obvious. Conclusion: DAC and AS2O3 had a synergetic effect for the HL-60 cell proliferation inhibition, apoptosis and expression of DAPK.

Highlights

Acute Leukemia (AL) is one of the common malignant tumors in China, originating from malignant clonal he-How to cite this paper: Ren, J.H., Yao, J.J., Guo, X.N., Guo, X.L. and Cai, S.X. (2015) The Effect of Decitabine Combined with Arsenic Trioxide on Death associated protein kinase (DAPK) Gene and HL-60 Cell Proliferation and Apoptosis
HL-60 cells were treated with different concentrations of DAC (20 μmol/L, 40 μmol/L, 80 μmol/L), AS2O3 (1 μmol/L, 2.5 μmol/L, 5 μmol/L) monotherapy for 24 h, 48 h, 72 h, along with the extension of the drug concentration and time, proliferation inhibition rate had gradually increased
The Effect of DAC and AS2O3 on Apoptosis of HL-60 Cell After HL-60 cells were treated with different concentrations of DAC (20 μmol/L, 40 μmol/L, 80 μmol/L), AS2O3 (1 μmol/L, 2.5 μmol/L, 5 μmol/L) monotherapy for 24 h, 48 h, 72 h, the apoptosis rate was gradually increased

Summary

Introduction

Acute Leukemia (AL) is one of the common malignant tumors in China, originating from malignant clonal he-How to cite this paper: Ren, J.H., Yao, J.J., Guo, X.N., Guo, X.L. and Cai, S.X. (2015) The Effect of Decitabine Combined with Arsenic Trioxide on DAPK Gene and HL-60 Cell Proliferation and Apoptosis. Acute Leukemia (AL) is one of the common malignant tumors in China, originating from malignant clonal he-. (2015) The Effect of Decitabine Combined with Arsenic Trioxide on DAPK Gene and HL-60 Cell Proliferation and Apoptosis. The hypermethylation of the gene promoter in human leukemia is related to the cell cycle regulation, apoptosis, adhesion between cells and DNA repair [1] [2], and the normal expression of gene silencing caused cancer. Different from gene mutations, DNA methylation is a biological process which can be reversible; the application of DNA methyltransferase (DNMT) inhibitors could make certain tumor gene demethylation, restoring its normal function. Aberrant methylation of promoter in carcinogenesis process is an early and frequent event, and it can be used as sensitive biomarkers of tumorigenesis

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