AZT对白血病细胞株KG-1a细胞增殖和端粒酶活性的影响

Effects of AZT on Leukemia Cell Line KG-1a Proliferation and Telomerase Activity

本研究探索端粒酶抑制剂3'-叠氮-2',3'-脱氧胸腺核苷(AZT)对人急性髓系白血病细胞株KG-1a细胞增殖和端粒酶活性的影响。用MTT法检测不同浓度AZT分别作用24、48、72 h时KG-1a细胞增殖水平;流式细胞术检测AZT对KG-1a细胞周期及细胞凋亡的影响;TRAP-PCR-ELISA法检测细胞端粒酶活性;RT-PCR法检测细胞端粒逆转录酶(hTERT)mRNA的表达。结果表明,AZT能抑制KG-1a细胞增殖,抑制作用具有时间和浓度依赖性;随AZT浓度的增加,处于S期的细胞数目减少,G2/M期细胞数目增加,且出现凋亡峰;AZT作用后实验组细胞的端粒酶活性降低,hTERT-mRNA表达下降,下调程度与AZT浓度呈正相关。结论:AZT在体外能明显抑制KG-1a细胞增殖,并诱导其凋亡,其机制与降低端粒酶活性、下调hTERT mRNA表达有关。

This study was purposed to investigate the effect of 3′-azido-2′,3′-dideoxythymidine（AZT）on the proliferation and telomerase activity of human acute myeloid leukemia cell line KG-1a.The effect of proliferation was detected by MTT assay after the KG-1a cell were stimulated for 24,48 and 72 h with different concentrations of AZT;telomerase activity was detected with TRAP-PCR-ELISA assay;RT-PCR was used to detect telomerase hTERT mRNA expression.The results showed that the proliferation of KG-1a cells was inhibited in a time and concentration dependent manner after exposure to AZT for 24,48 and 72 h;the KG-1a cells decreased in S phase and increased in G2/M phase with the increasing of the concentration of AZT;telomerase activity and hTERT-mRNA expression in the experimental groups decreased after treated with AZT,which was positilvely correlated with concentration of AZT.It is concluded that AZT inhibits KG-1a cell proliferation and induces apoptosis,which maybe related with its decreasing the telomerase activity and hTERT mRNA expression.