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


CONCLUSIONS
These results may provide a new insight into the molecular mechanism of 5-Fu in therapy of breast cancer.
Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061, China.
J
J
Cai
S
S
Chen
W
W
Zhang
Y
Y
Wei
J
J
Lu
J
J
Xing
Y
Y
Dong
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D015180:Electrophoresis, Gel, Two-Dimensional; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D040901:Proteomics; D060888:Real-Time Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil