Histone deacetylase inhibitors sensitize 5‑fluorouracil‑resistant MDA‑MB‑468 breast cancer cells to 5‑fluorouracil

  • Authors:
    • Tetsuya Minegaki
    • Ai Suzuki
    • Misato Mori
    • Shiori Tsuji
    • Satoshi Yamamoto
    • Airi Watanabe
    • Tomoyo Tsuzuki
    • Takaki Tsunoda
    • Asuka Yamamoto
    • Masayuki Tsujimoto
    • Kohshi Nishiguchi
  • View Affiliations

  • Published online on: September 4, 2018     https://doi.org/10.3892/ol.2018.9388
  • Pages: 6202-6208
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Abstract

Resistance to 5‑fluorouracil (5‑FU) is a serious problem in cancer therapy and overcoming it is required in order to improve the efficacy of cancer chemotherapy. Histone deacetylase (HDAC) inhibitors are used in cancer treatments and, recently, it has been reported that HDAC inhibitors can overcome resistance to various anti‑cancer drugs in vitro. In the present study, a 5‑FU‑resistant breast cancer cell line was established, and the effects of HDAC inhibitors in these cells were examined. The 5‑FU‑resistant cell line MDA‑MB‑468 (MDA468/FU) was established by continuous exposure of the parental cells to 5‑FU. This subline was characterized by high resistance to 5‑FU, higher mRNA expression levels of thymidylate synthetase and dihydropyrimidine dehydrogenase (DPD), and lower mRNA expression levels of uridine monophosphate synthetase (UMPS) than the parental cells. Gimeracil, a DPD inhibitor, did not affect the sensitivity of MDA468/FU cells to 5‑FU. Oteracil, a UMPS inhibitor, decreased the cytotoxicity of 5‑FU in MDA468 cells, but not in MDA468/FU cells. The HDAC inhibitors, valproic acid and suberanilohydroxamic acid sensitized the two cell lines to 5‑FU in a concentration‑dependent manner. In conclusion, the results of the present study revealed that HDAC inhibitors increase the sensitivity to 5‑FU in 5‑FU‑sensitive and ‑resistant cells.
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November-2018
Volume 16 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Minegaki T, Suzuki A, Mori M, Tsuji S, Yamamoto S, Watanabe A, Tsuzuki T, Tsunoda T, Yamamoto A, Tsujimoto M, Tsujimoto M, et al: Histone deacetylase inhibitors sensitize 5‑fluorouracil‑resistant MDA‑MB‑468 breast cancer cells to 5‑fluorouracil. Oncol Lett 16: 6202-6208, 2018
APA
Minegaki, T., Suzuki, A., Mori, M., Tsuji, S., Yamamoto, S., Watanabe, A. ... Nishiguchi, K. (2018). Histone deacetylase inhibitors sensitize 5‑fluorouracil‑resistant MDA‑MB‑468 breast cancer cells to 5‑fluorouracil. Oncology Letters, 16, 6202-6208. https://doi.org/10.3892/ol.2018.9388
MLA
Minegaki, T., Suzuki, A., Mori, M., Tsuji, S., Yamamoto, S., Watanabe, A., Tsuzuki, T., Tsunoda, T., Yamamoto, A., Tsujimoto, M., Nishiguchi, K."Histone deacetylase inhibitors sensitize 5‑fluorouracil‑resistant MDA‑MB‑468 breast cancer cells to 5‑fluorouracil". Oncology Letters 16.5 (2018): 6202-6208.
Chicago
Minegaki, T., Suzuki, A., Mori, M., Tsuji, S., Yamamoto, S., Watanabe, A., Tsuzuki, T., Tsunoda, T., Yamamoto, A., Tsujimoto, M., Nishiguchi, K."Histone deacetylase inhibitors sensitize 5‑fluorouracil‑resistant MDA‑MB‑468 breast cancer cells to 5‑fluorouracil". Oncology Letters 16, no. 5 (2018): 6202-6208. https://doi.org/10.3892/ol.2018.9388