Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell line

Katsuyuki Takahashi, Masako Tanaka, Azusa Inagaki, Hideki Wanibuchi, Yasukatsu Izumi, Katsuyuki Miura, Katsuya Nagayama, Masayuki Shiota*, Hiroshi Iwao

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Triple-negative breast cancers (TNBCs) are defined as tumors that lack expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Clinically, TNBC patients are treated with cytotoxic drugs including 5-fluorouracil (5-FU). However, TNBCs develop resistance to such drugs after a series of treatments. To elucidate the mechanisms of drug resistance, establishment of drug-resistant cancer cell lines should be one of the most useful model systems. However, 5-FU-resistant TNBC cell lines have not been previously reported. In this study, we established a 5-FU-resistant cell line, MDA-MB-231/5-FU, from the human TNBC cell line MDA-MB-231, by repeated exposure to stepwise increases in the concentration of 5-FU. The IC50 value of 5-FU for MDA-MB-231/5-FU was 5.5-fold that for the parental cells. The MDA-MB-231/5-FU cell line acquired resistance to not only 5-FU, but also vinorelbine, paclitaxel and gemcitabine. Additionally, we performed iTRAQ-based quantitative proteomics in MDA-MB-231/5-FU cells and the parental cells in order to characterize MDA-MB-231/5-FU. The proteins upregulated in the newly established cells were mainly classified into the categories of 'DNA recombination', 'cell cycle', 'complex assembly', 'cytoskeleton organization', 'transport' and 'negative regulation of cell death'. These proteins may be related to mechanisms of drug resistance in TNBCs. Our established MDA-MB-231/5-FU cell line should be a useful tool for identifying new mechanisms of drug resistance and new drug targets in TNBCs.

Original languageEnglish
Pages (from-to)1985-1991
Number of pages7
JournalInternational journal of oncology
Issue number6
Publication statusPublished - 2013 Dec
Externally publishedYes


  • 5-fluorouracil
  • Drug-resistant cell
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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