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

  • Guopei Zheng
  • Fang Peng
  • Renkui Ding
  • Yanhui Yu
  • Yongmei Ouyang
  • Zhuchu Chen
  • Zhiqiang Xiao
  • Zhimin He
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

Authors and Affiliations

  • Guopei Zheng
    • 1
  • Fang Peng
    • 2
  • Renkui Ding
    • 1
  • Yanhui Yu
    • 1
  • Yongmei Ouyang
    • 1
  • Zhuchu Chen
    • 1
    • 2
  • Zhiqiang Xiao
    • 2
  • Zhimin He
    • 1
  1. 1.Cancer Research Institute, Xiangya School of MedicineCentral South UniversityChangshaPeople’s Republic of China
  2. 2.Key Laboratory of Cancer Proteomics of Ministry of Health of China, Xiangya HospitalCentral South UniversityChangshaPeople’s Republic of China