Journal of Cancer Research and Clinical Oncology

, Volume 136, Issue 10, pp 1477–1488

Identification of proteins responsible for the multiple drug resistance in 5-fluorouracil-induced breast cancer cell using proteomics analysis

Authors

  • Guopei Zheng
    • Cancer Research Institute, Xiangya School of MedicineCentral South University
  • Fang Peng
    • Key Laboratory of Cancer Proteomics of Ministry of Health of China, Xiangya HospitalCentral South University
  • Renkui Ding
    • Cancer Research Institute, Xiangya School of MedicineCentral South University
  • Yanhui Yu
    • Cancer Research Institute, Xiangya School of MedicineCentral South University
  • Yongmei Ouyang
    • Cancer Research Institute, Xiangya School of MedicineCentral South University
  • Zhuchu Chen
    • Cancer Research Institute, Xiangya School of MedicineCentral South University
    • Key Laboratory of Cancer Proteomics of Ministry of Health of China, Xiangya HospitalCentral South University
  • Zhiqiang Xiao
    • Key Laboratory of Cancer Proteomics of Ministry of Health of China, Xiangya HospitalCentral South University
    • Cancer Research Institute, Xiangya School of MedicineCentral South University
Original Paper

DOI: 10.1007/s00432-010-0805-z

Cite this article as:
Zheng, G., Peng, F., Ding, R. et al. J Cancer Res Clin Oncol (2010) 136: 1477. doi:10.1007/s00432-010-0805-z

Abstract

Purpose

This study aimed to explore the mechanism of multi-drug resistance (MDR) in 5-fluorouracil (5-FU)-induced breast cancer cell MCF-7.

Methods

MCF-7 cells were exposed in stepwise escalating concentration of 5-FU to develop the resistant cell line, MCF-7/5-FU. Biological and molecular characteristics of the cells were studied through MTT, flow cytometry, real-time PCR, western-blot, and the global protein profiles between MCF-7/5-FU and parental MCF-7 were compared using proteomic approach. Then some of the differentially expressed proteins were validated by western-blot. In addition, the role of 14-3-3σ was validated using gene transfection.

Results

Drug resistance of MCF-7/5-FU cells to 5-FU, MX, cDDP, ADM, TAXOL all increased significantly compared with MCF-7 cells and that maybe related to BCRP, but not MDR1 and MRP1. Differentially expressed proteins between MCF-7/5-FU and MCF-7 cells were identified; 12 proteins were up-regulated and 18 proteins were down-regulated in MCF-7/5-FU cells. Expressive levels of some proteins in western-blot validation were consistent with the results in proteomic analysis. Enforced 14-3-3σ expression can increase the sensitivity of MCF-7/5-FU cells to 5-FU and cDDP.

Conclusion

MDR of MCF-7/5-FU likely associated with differentially expressed proteins and 14-3-3σ may play a positive role in chemotherapy. These findings may provide theoretical support for the prediction of chemotherapeutic response and reverse of MDR.

Keywords

5-FluorouracilProteomics analysisMDRBreast cancer14-3-3σ

Abbreviation

5-FU

5-Fluorouracil

MX

Mitoxantrone

cDDP

Cisplatin

ADM

Adramycin

BCRP

Breast cancer resistance protein

MDR1

P-glycoprotein

MRP1

Multidrug resistance-associated protein

2-DE

Two-dimensional gel electrophoresis

MALDI-TOF–MS

Matrix-assisted laser desorption/ionization-time of flight mass spectrometry

MDR

Multi-drug resistance

Copyright information

© Springer-Verlag 2010