Role of trichostatin A in proliferation of human lung adenocarcinoma cell line NCI-H1299 and its mechanism / 中国癌症杂志

ABSTRACT

Background and purpose: Trichostatin A (TSA), an antifungal antibiotic with cytostatic and differentiating properties in mammalian cell culture, is a potent and specific inhibitor of histone deacetylase (HDAC). This study was aimed to investigate the influence of trichostatin A on the growth of human lung adenocacinoma cells in vitro, and to explore the mechanisms involved. Methods: MTT assay was employed to evaluate the inhibitory effect of TSA (0.1, 0.2,0.4 μmol/L) on the growth of human NCI-H1299 cancer cells. The cell cycle distribution and apoptotic ratio were determined by flow cytometry. The acetyl level of histone H4 after TSA treatment was detected by Western blot;the mRNA level of Bax,Bcl-2,p21 and cyelinBl was measured by Real-time PCR. Results: TSA inhibited the growth of NCI-H1299 cells in a dose-and time-dependent manner. Flow cytometry showed that the cells were blocked at G_2/M phase and cell apoptosis was increased compared to the control. TSA significantly increased the acetyl level of histone H4, induced p21 and Bax expression, and inhibited the expression of cyclin BI and Bcl-2. Conclusion: TSA inhibits the growth of lung cancer cells in vitro through inducing cell apoptosis and cell cycle arrest, which might be related to its regulatory effects on the acetyl blot of histone and the expression of p21, Bax, Bcl-2 and cyclinBl.