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

Area of Science:

• Oncology
• Molecular Biology
• Proteomics

Background:

• Multi-drug resistance (MDR) is a major challenge in breast cancer chemotherapy.
• Understanding the molecular mechanisms of MDR is crucial for developing effective treatment strategies.

Purpose of the Study:

• To explore the mechanism of multi-drug resistance (MDR) in 5-fluorouracil (5-FU)-induced breast cancer cell line MCF-7.
• To identify differentially expressed proteins associated with MDR.
• To investigate the role of 14-3-3sigma in modulating chemotherapy sensitivity.

Main Methods:

• Developed a 5-fluorouracil (5-FU)-resistant MCF-7 cell line (MCF-7/5-FU).
• Utilized MTT assays, flow cytometry, real-time PCR, and western-blotting for biological and molecular characterization.
• Employed proteomic analysis to compare protein profiles between resistant and parental cells.
• Validated key protein expressions and investigated the function of 14-3-3sigma via gene transfection.

Main Results:

• MCF-7/5-FU cells exhibited significantly increased resistance to 5-FU and other chemotherapeutic agents, potentially linked to BCRP expression.
• Proteomic analysis identified 12 up-regulated and 18 down-regulated proteins in MCF-7/5-FU cells compared to MCF-7 cells.
• Enforced expression of 14-3-3sigma enhanced the sensitivity of MCF-7/5-FU cells to 5-FU and cisplatin (cDDP).

Conclusions:

• The MDR in MCF-7/5-FU cells is associated with differentially expressed proteins.
• 14-3-3sigma plays a positive role in chemotherapy, suggesting its potential as a therapeutic target.
• These findings provide a theoretical basis for predicting chemotherapeutic response and reversing MDR.