Inhibition of heat shock protein 27 phosphorylation promotes sensitivity to 5‑fluorouracil in colorectal cancer cells

Matsunaga,Atsushi; Ishii,Yoshiyuki; Tsuruta,Masashi; Okabayashi,Koji; Hasegawa,Hirotoshi; Kitagawa,Yuko

doi:10.3892/ol.2014.2580

Inhibition of heat shock protein 27 phosphorylation promotes sensitivity to 5‑fluorouracil in colorectal cancer cells

Authors:
- Atsushi Matsunaga
- Yoshiyuki Ishii
- Masashi Tsuruta
- Koji Okabayashi
- Hirotoshi Hasegawa
- Yuko Kitagawa
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Affiliations: Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan
Published online on: October 1, 2014 https://doi.org/10.3892/ol.2014.2580
Pages: 2496-2500

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Abstract

The aim of the present study was to investigate whether the inhibition of HSP27 phosphorylation, which affects certain cellular functions, modulates sensitivity to 5‑fluorouracil (5‑FU) in colorectal cancer cells. Exposure to 5‑FU in HCT116 and HCT15 cells expressing high levels of HSP27 with a low 5‑FU sensitivity caused a minimal change in HSP27 expression, but induced the upregulation of HSP27 phosphorylation, particularly at Ser78. By contrast, exposure to 5‑FU in HT29 cells expressing a low level of HSP27 with a high 5‑FU sensitivity marginally increased HSP27 expression, with minimal phosphorylation. Treatment with a selective inhibitor, p38 mitogen‑activated protein kinase (MAPK; SB203580), caused the dose‑dependent suppression of HSP27 phosphorylation, which was upregulated by 5‑FU, reducing the half maximal inhibitory concentration values of 5‑FU in the HCT116 and HCT15 cells. However, treatment with SB203580 exhibited no significant effect on cell growth or survival. In conclusion, this study indicated that the inhibition of HSP27 phosphorylation by a selective inhibitor of p38 MAPK promotes 5‑FU sensitivity without causing cytotoxicity in colorectal cancer cells.

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