OBJECTIVETo investigate the inhibitory effect of decitabine (DAC) in various dosages on the proliferention of MDS-RAEB cell line MDS-L and its mechanism.

METHODSLC-MS/MS method was used to test the blood DAC concentration of 2 groups of MDS patients being treated with DAC 20 and 15 mg/m×5 d. In according to the various blood DAC concentration levels, the MDS-L cells were treated with different DAC dosages for 24, 48, 72 and 96 h, respectively. The CCK-8 method was applied to determine the cell proliferation, the flow cytometry was used to analyze the cell cycle and cell apoptosis changes, the P15DNA methylation status was measured by methylation specific PCR using EZ DNA Methylation-Gold Kit.

RESULTSThe blood DAC concentration of MDS patients treated with DAC 20 mg/m×5 d was 174.08±80.15(84.7-311) ng/ml, which was significantly higher than 89.87±32.94(43.2-165)ng/ml for the group treated with 15 mg/m×5 d (P=0.014). DAC could notably inhibit the proliferation of MDS-L cells, and the effect was in dose- and- time-dependent manner(r=0.786). However, when DAC concentration was ≥0.1 µg/ml, the proliferation inhibition rates were not significantly different between various dosages. After DAC treatment, MDS-L cells in Gphase increased notably, while cells in S phase decreased significantly. Also, the P15DNA methylation status of MDS-L cells decreased after being treated with DAC for 96 h, but the difference was not significant between various dosages.

CONCLUSIONDAC can significantly suppress MDS-L cell proliferation, block MDS-L cells in Gphase and induce the apoptosis at low concentration (0.1-0.2 µg/ml).