Downregulation of growth differentiation factor-15 in trichostatin A-induced apoptosis could play a role in progression of gastric cancer

Int J Clin Exp Pathol. 2015 Jul 1;8(7):8136-42. eCollection 2015.

Abstract

Aim: To investigate the effect of trichostatin A (TSA) on gastric cancer cell line BGC-823, and identify the differentially expressed genes induced by TSA, which might participate in the progression of gastric cancer.

Methods: MTT, fluorescence microscopy, and flow cytometry were used to detect the effect of TSA on growth inhibition and apoptosis of BGC-823 cells. Using gene microarray, we analyzed the changes in gene expression. Change in growth differentiation factor-15 (GDF-15) was verified by qRT-PCR and Western blotting. The expression of GDF-15 in gastric cancer and adjacent normal tissues was detected by immunohistochemistry.

Results: Apoptosis of BGC-823 cells induced by TSA (75 ng/mL for 48 h) was demonstrated by flow cytometry. There were significant variations between TSA treated groups and control groups (P = 0.02). Nuclear chromatin condensation and fluorescence intensity were observed by fluorescence microscopy. GDF-15 gene expression and protein level were significantly reduced in the TSA treated group (75 ng/mL for 48 h). Immunohistochemistry demonstrated that the expression of GDF-15 in gastric adenocarcinoma was significantly higher than in the surrounding normal tissues (P < 0.05).

Conclusion: Lower GDF-15 gene expression due to TSA-induced apoptosis was found in gastric cancer cell line BGC-823. Higher GDF-15 gene expression was seen in gastric adenocarcinoma tissues.

Keywords: BGC-823; Gastric cancer; apoptosis; growth differentiation factor-15; trichostatin A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disease Progression
  • Down-Regulation
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Growth Differentiation Factor 15 / genetics
  • Growth Differentiation Factor 15 / metabolism*
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Immunohistochemistry
  • Oligonucleotide Array Sequence Analysis
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Hydroxamic Acids
  • trichostatin A