title: [Inhibitory effect of trichostatin A on HepG2 cell proliferation and the mechanisms].
abstract: OBJECTIVE
  To investigate the inhibitory effect of trichostatin A (TSA) on the proliferation of HepG2 cells and explore the underlying mechanism.
  
  
  METHODS
  HepG2 cells exposed to different concentrations of TSA for 24, 48, or 72 h were examined for cell growth inhibition using a cell counting kit, changes in cell cycle distribution with flow cytometry, cell apoptosis with annexin V-FTIC/PI double staining, and cell morphology changes under inverted microscope. The expressions of beta-catenin, HDAC1, HDAC3, H3K9, cyclinD1 and Bax proteins in the exposed cells were detected by Western blotting, and the expressions of HDAC1 and HDAC3 mRNAs by quantitative fluorescent PCR.
  
  
  RESULTS
  Exposure to TSA caused significant dose- and time-dependent inhibition of HepG2 cell proliferation (P<0.05) and resulted in increased cell percentage in G0/G1 and G2/M phases and decreased cell percentage in S phase. The apoptotic index in the control group was (6.22 ± 0.25)%, which increased to (7.17 ± 0.20)% and (18.14 ± 0.42)% after exposure to 250 and 500 nmol/L TSA, respectively. Exposure to 250 and 500 nmol/L TSA also caused cell morphology changes with numerous floating cells. The expressions of beta-catenin, H3K9 and Bax proteins were significantly increased and CyclinD1, HDAC1, and HDAC3 protein expressions decreased in TSA-treated cells, but the expressions of HDAC1 and HDAC3 mRNAs showed no significant changes.
  
  
  CONCLUSIONS
  TSA can inhibit the proliferation of HepG2 cells and induce cell cycle arrest and apoptosis by inhibiting HDAC activity, promoting histone acetylation, and activating Wnt/beta-catenin signaling pathway.
authors: Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 400016, China. E-mail: 569770664@qq.com.
authors: Qingqiang
authors: Q
authors: Shi
authors: Guowei
authors: G
authors: Zuo
authors: Ziqiang
authors: Z
authors: Feng
authors: Lücui
authors: L
authors: Zhao
authors: Nian
authors: N
authors: Luo
authors: Zhimei
authors: Z
authors: You
authors: Jing
authors: J
authors: Xia
authors: Danyang
authors: D
authors: Li
authors: Jing
authors: J
authors: Li
authors: Dilong
authors: D
authors: Chen
mesh_terms: D000107:Acetylation; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D056945:Hep G2 Cells / Q000187:drug effects; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D060449:Wnt Signaling Pathway; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D000099186:Histone Deacetylase 3
chemical_list: D019938:Cyclin D1; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D006657:Histones; D006877:Hydroxamic Acids; D051028:bcl-2-Associated X Protein; D051176:beta Catenin; D000099186:Histone Deacetylase 3; C494826:BAX protein, human; C530104:CCND1 protein, human; C495270:CTNNB1 protein, human; C012589:trichostatin A; C110550:HDAC1 protein, human