TY - JOUR
T1 - Inhibition of heat shock protein 27 phosphorylation promotes sensitivity to 5-fluorouracil in colorectal cancer cells
AU - Matsunaga, Atsushi
AU - Ishii, Yoshiyuki
AU - Tsuruta, Masashi
AU - Okabayashi, Koji
AU - Hasegawa, Hirotoshi
AU - Kitagawa, Yuko
N1 - Publisher Copyright:
© Spandidos Publications 2014. All rights reserved.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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.
AB - 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.
KW - 5-fluorouracil
KW - Colorectal cancer
KW - Heat shock protein 27 (HSP27)
KW - Phosphorylation
KW - Sensitivity
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U2 - 10.3892/ol.2014.2580
DO - 10.3892/ol.2014.2580
M3 - Article
AN - SCOPUS:84908024646
VL - 8
SP - 2496
EP - 2500
JO - Oncology Letters
JF - Oncology Letters
SN - 1792-1074
IS - 6
ER -