Proteomic analysis of pancreatic ductal carcinoma cells after combined treatment with gemcitabine and trichostatin A

J Proteome Res. Nov-Dec 2005;4(6):1909-16. doi: 10.1021/pr050154j.

Abstract

The human pancreatic adenocarcinoma cell line T3M4 has been treated with two agents, gemcitabine (2',2'-difluorodeoxycytidine, a drug interfering with DNA synthesis) and trichostatin A (a drug interfering with histone acetylation), both separately and in association. The association of the two drugs showed a marked cooperative effect in inhibiting proliferation and inducing apoptosis of the cells. In an effort to identify differentially expressed proteins in the different drug treatments, the proteomic expression has been studied by two-dimensional gel electrophoresis comparing untreated cells with cells treated with trichostatin A and/or gemcitabine. A total of 81 differentially expressed polypeptide chains have been visualized by setting a 2.5-fold threshold value. Of these, 56 were identified via MALDI-TOF and Q-TOF MS analyses. Most of the regulated proteins are involved in two major biological processes, namely apoptotic cell death and proliferation. Our results demonstrate that the level of activation/repression of the proteins involved in these processes correlates with the growth inhibition and the apoptotic response of the cells subjected to single or combined drug treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis
  • Carcinoma, Pancreatic Ductal / drug therapy*
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA / chemistry
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Dose-Response Relationship, Drug
  • Electrophoresis, Gel, Two-Dimensional
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hydroxamic Acids / administration & dosage*
  • Hydroxamic Acids / pharmacology
  • Inhibitory Concentration 50
  • Mass Spectrometry
  • Peptides / chemistry
  • Protein Binding
  • Protein Synthesis Inhibitors / administration & dosage
  • Proteins / chemistry
  • Proteome
  • Proteomics / methods*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Time Factors

Substances

  • Antibiotics, Antineoplastic
  • Hydroxamic Acids
  • Peptides
  • Protein Synthesis Inhibitors
  • Proteins
  • Proteome
  • Deoxycytidine
  • trichostatin A
  • DNA
  • gemcitabine