title: [Decitabine inhibits cell proliferation and induces apoptosis of all-trans retinoid acid-resistant acute promyelocytic leukemia NB4-R2 cell line].
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.
authors.affiliation: Department of Hematology, ThirSun Yat-Sen University, Guangzhou, Guangdong Province, China.
authors.forename: Mu-Jun
authors.initials: MJ
authors.lastname: Xiong
authors.forename: Ruo-Zhi
authors.initials: RZ
authors.lastname: Xiao
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Chen
authors.forename: Zi-Jie
authors.initials: ZJ
authors.lastname: Long
authors.forename: Xing
authors.initials: X
authors.lastname: Wu
authors.forename: Dong-Jun
authors.initials: DJ
authors.lastname: Lin
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D000077209:Decitabine; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D014212:Tretinoin; D000077209:Decitabine; D001374:Azacitidine