[Analysis of in vitro anti-leukemia effect of 5-aza-2'-deoxycitydine].
OBJECTIVE
To investigate the effect of methylation transferase inhibitor 5-aza-2'-deoxycitydine (5-aza-2 dC) on the growth, differentiation and apoptosis of human acute myeloid leukemia(AML) cell line HL-60, and to explore the possible anti-leukemia mechanism of 5-aza-2 dC.


METHODS
HL-60 cells were treated by 5-aza-2 dC at various concentrations for different periods of time. The effect of 5-aza-2 dC on the growth of HL-60 cells were detected by MTT assay. The effect on the cell cycle and differentiation were detected by flow cytometry. The effect on the apoptosis were detected by Hochest33342 staining and flow cytometry. The expression of S100A8 and S100A9 was detected by reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
(1) 5-aza-2 dC inhibited the growth of HL-60 cells in a concentration- and time-dependent manner, and HL-60 cells were arrested at G2/M phases; (2) 5-aza-2 dC enhanced the expression of cell differentiation antigen CD11b at HL-60 cells, especially at the low drug concentration; (3) 5-aza-2 dC induced HL-60 cell apoptosis in a concentration- and time-dependent manner, especially at the high drug concentration; (4) 5-aza-2 dC increased the expression levels of S100A8 and S100A9 mRNA in HL-60 cells.


CONCLUSIONS
5-aza-2 dC can inhibit the growth of HL-60 cells accompanied with G2/M phase arrest, induce the differentiation and apoptosis of the cells, and increase the expression levels of S100A8 and S100A9 mRNA, which may be the anti-AML mechanism of 5-aza-2 dC.
Xiao
Yan-hua
YH
Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, China.
Yi
Hong
H
Tan
Tan
T
Liang
Ting
T
Chen
Zhu-chu
ZC
Xiao
Zhi-qiang
ZQ
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D040501:Calgranulin A / Q000096:biosynthesis / Q000235:genetics; D040502:Calgranulin B / Q000096:biosynthesis / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D000077209:Decitabine; D018922:HL-60 Cells; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D000964:Antimetabolites, Antineoplastic; D040501:Calgranulin A; D040502:Calgranulin B; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine