J Cai1, S Chen, W Zhang, Y Wei, J Lu, J Xing, Y Dong. 1. Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061, China.
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.
BACKGROUND:5-Fluorouracil (5-Fu) is a commonly used chemotherapeutic agent in clinical care of breast cancerpatients. 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 humanbreast 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.