Trichostatin A inducing apoptosis and cell cycle arrest of bladder cancer cells:the in vitro mechanism

Objective:To investigate the influence of trichostatin A(TSA),a histone deacetylase(HDAC) inhibitor,on the growth of human bladder cancer cells and on the expression of related genes,and to explore the mechanism involved.Methods: MTT assay was employed to evaluate the inhibitory effect of TSA(0.05,0.1,0.2,0.4,0.8 μmol/L)on growth of human T24 bladder cancer cells.The morphological changes of T24 cells were observed by transmission electron microscope after treated with 0.4 μmol/L TSA; the cell cycle distribution and apoptotic ratio were determined by flow cytometry.The acetyl level of histone after TSA treatment was detected by Western blot;the mRNA expression of p21CIP1/WAF1,cyclin A,and cyclin E was measured by FQ-PCR.Results: MTT assay revealed TSA inhibited the growth of T24 cells in a concentration-and time-dependent manner.Typical morphological changes of apoptotic cells were observed by electron microscope after treatment with 0.4 μmol/L TSA.Flow cytometry showed that the cells were blocked at G_0/G_1 phase and typical Sub-G_1 peak appeared.TSA obviously promoted the acetyl level of histone,induced expression of p21CIP1/WAF1 mRNA,and inhibited expression of cyclin A,but had no obvious influence on expression of cyclin E.Conclusion: TSA can inhibit bladder cancer cells through inducing cell apoptosis and cell cycle arrest in vitro,which might be related to the acetyl level of histone and the expression of p21CIP1/WAF1 and cyclin A.