Preliminary Study. Histone Deacetylase Inhibitor Sodium Phenylbutyrate Induced Cell Cycle Arrest Of Human Leukemia Cell Lines And Molecular Mechanisms

Histone deacetylase inhibitors showed broad spectum anti-tumor activity. They showed targeted anti-tumor activity through increasing histone acetylation. A serial researches had revealed they had potent effects on apoptosis, growth arrest and differentiation in vitro in various malignant tumor cell lines, such as U937. It had been revealed that histone deacetylase inhibitors arrested the cell cycle progression associated with up-regulated p21WAF1/CIP1 through transcription factor SP1.PML-RARα and AML1-ETO, which resulted from chrosome translocation t(8;21) and t(15;17), were implicated in leukemogenesis and were associated with a distinct type of leukemia. It had been revealed that both of them could abnormally recruit histone deacetylase and repress genes expression associated with hemapoietic cell differentiation. HDAC inhibitors could reverse these abnormalities and impose anti-leukemia ability. HDAC inhibitors could treat Kasumi-1 and NB4 cell lines, who had AML1-ETO and PML-RARα fusion proteins respectively, not only through reversing fusion proteins' abnormalities, but also through mechanisms independent on fusion proteins, such as arrest cell cycle by up-regulating p21WAF1/CIP1. It had not been known whether there were interaction between these two mechanism.In the first part of our thesis, we investigated effects of HDAC inhibitors on cell cycle in Kasumi-1 and NB4 cell lines. And we explored molecular mechanism. We found that PB could inhibit cell cycle of Kasumi-1 and NB4 cell lines, just like U937. G0/G1 phase arrest and S-phase content reduction were observed. After U937, Kasumi-1 and NB4 cell lines exposed to 1mmol/L PB for 72 hrs, G0/G1 -phase...