title: Inhibition of heat shock protein 27 phosphorylation promotes sensitivity to 5-fluorouracil in colorectal cancer cells.
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.
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Matsunaga
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Tsuruta
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Okabayashi
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
keywords: 5-fluorouracil; colorectal cancer; heat shock protein 27 (HSP27); phosphorylation; sensitivity