Proteomic analysis of differentially expressed proteins in 5-fluorouracil-treated human breast cancer MCF-7 cells

Clin Transl Oncol. 2014 Jul;16(7):650-9. doi: 10.1007/s12094-013-1127-9. Epub 2013 Nov 12.

Abstract

Background: 5-Fluorouracil (5-Fu) is a commonly used chemotherapeutic agent in clinical care of breast cancer patients. However, the mechanism of how the 5-Fu works is complex and still largely unknown.

Objective: The objective of this study was to understand the mechanism further and explore the new targets of 5-Fu.

Methods: The differentially expressed proteins induced by 5-Fu in human breast cancer MCF-7 cells were identified by proteomic analysis. Four differentially expressed proteins were validated using Western blot and quantitative real-time reverse-transcription polymerase chain reaction analysis for protein and mRNA levels. The effect of 5-Fu on MCF-7 cells was determined by cell viability assay, transmission electron microscopy and flow cytometry analysis.

Results: 5-Fu dose-dependently inhibited cell proliferation with the IC50 value of 98.2 μM. 5-Fu also induced obviously morphological change and apoptosis in MCF-7 cells. Twelve differentially expressed proteins involved in energy metabolism, cytoskeleton, cellular signal transduction and tumor invasion and metastasis were identified.

Conclusion: These results may provide a new insight into the molecular mechanism of 5-Fu in therapy of breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Blotting, Western
  • Breast Neoplasms / metabolism*
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects*
  • Electrophoresis, Gel, Two-Dimensional
  • Flow Cytometry
  • Fluorouracil / pharmacology*
  • Humans
  • MCF-7 Cells
  • Proteomics
  • Real-Time Polymerase Chain Reaction
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Antimetabolites, Antineoplastic
  • Fluorouracil