Decitabine inhibits cell proliferation and induces apoptosis of all-trans retinoid acid-resistant acute promyelocytic leukemia NB4-R2 cell line.
- Author:
Mu-Jun XIONG
1
;
Ruo-Zhi XIAO
;
Yan CHEN
;
Jia-Jie CHEN
;
Zi-Jie LONG
;
Xing WU
;
Dong-Jun LIN
Author Information
1. Department of Hematology, ThirSun Yat-Sen University, Guangzhou, Guangdong Province, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
drug effects;
Azacitidine;
analogs & derivatives;
pharmacology;
Cell Line, Tumor;
Cell Proliferation;
drug effects;
Drug Resistance, Neoplasm;
Humans;
Leukemia, Promyelocytic, Acute;
metabolism;
pathology;
Tretinoin;
pharmacology
- From:
Journal of Experimental Hematology
2012;20(1):48-52
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study was to investigate the proliferation-inhibitory and inducing apoptotic effects of decitabine (DAC) on acute promyelocytic leukemia NB4-R2 cells. Cell inhibitory rate was determined by cell proliferation and cytotoxicity assay (WST-1 assay) after NB4-R2 cells were treated with 0.01 - 0.5 µmol/L DAC for 24, 48 and 72 h. Apoptosis of NB4-R2 cells treated with 0.05 - 5 µmol/L DAC for 48 h was detected by flow cytometry with PI staining and AnnexinV/PI staining. Reverse transcription-PCR (RT-PCR) was used to determine the mRNA expression level of MDR1 gene encoding P-glycoprotein (P-gp). The results indicated that DAC (0.01 - 0.5 µmol/L) inhibited the proliferation of NB4-R2 cells in both time- and concentration-dependent manners. The IC(50) of DAC on the viability of NB4-R2 cells after treatment for 48 and 72 h were 0.089 and 0.064 µmol/L respectively. DAC (0.05 - 5 µmol/L) induced NB4-R2 cell apoptosis in dose-dependent manner with down-regulation of MDR 1 gene expression. It is concluded that a low concentration of DAC (< 0.5 µmol/L) inhibits cell proliferation, while higher concentration of DAC (1 or 5 µmol/L) induces apoptosis on NB4-R2 cells, accompanied with reduction of MDR1 levels.
