曲古抑菌素A诱导MOLT-4细胞凋亡的机制

Mechanism of Cell Cycle Arrest and Apoptosis of MOLT-4 Induced by TSA

目的通过研究曲古抑菌素A(trichostatin A,TSA)作用前后MOLT-4细胞基因表达谱的差异,初步探讨TSA诱导细胞周期阻滞和凋亡的机制。方法TSA以不同浓度和不同作用时间作用MOLT-4细胞,通过流式细胞仪检测其凋亡率的变化。提取细胞RNA,应用基因芯片方法分析TSA作用前后的基因表达变化,RT-PCR验证芯片结果的可靠性。结果MOLT-4细胞对TSA非常敏感,纳摩尔级水平即可诱导显著的细胞凋亡,而且这种凋亡与TSA作用浓度及时间呈现明显的线性关系。基因芯片结果显示,200nmol/LTSA作用MOLT-424h后共有952个基因发生不同程度的变化,其中上调的有477种,下调的有475种,部分结果经RT-PCR证实。结论TSA诱导肿瘤细胞周期阻滞和凋亡是一个多基因参与的复杂过程。

Objective To explore the mechanism of cell cycle arrest and apoptosis of MOLT-4 induced by trichostatin A （TSA） by studying the difference in gene expression profile of MOLT-4 cells treated with TSA. Methods MOLT-4 cells were treated with different concentrations of TSA for different time. The apoptotic rate was detected by flow cytometry, the changes in gene expression before and after treatment with TSA were analyzed by using microarray and the results were identified by RT-PCR. Results MOLT-4 cells were very sensitive to TSA. nmol/L TSA could induce significant cell apoptosis in a time-and concentration-dependent manner. The results of microarray revealed after treatment of MOLT-4 cell with 200 nmol/L TSA for 24 h, 952 genes changed to varying degrees, including 477 up-regulated and 475 down regulated. Conclusion Multiple genes are involved in the TSA-induced cell cycle arrest and apoptosis of MOLT-4 cells.