Suppression of heat shock protein 27 expression promotes 5-fluorouracil sensitivity in colon cancer cells in a xenograft model

Hayashi,Ryohei; Ishii,Yoshiyuki; Ochiai,Hiroki; Matsunaga,Atsushi; Endo,Takashi; Hasegawa,Hirotoshi; Kitagawa,Yuko

doi:10.3892/or.2012.1935

Suppression of heat shock protein 27 expression promotes 5-fluorouracil sensitivity in colon cancer cells in a xenograft model

Authors:
- Ryohei Hayashi
- Yoshiyuki Ishii
- Hiroki Ochiai
- Atsushi Matsunaga
- Takashi Endo
- Hirotoshi Hasegawa
- Yuko Kitagawa
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Affiliations: Department of Surgery, School of Medicine, Keio University, Tokyo 160-8582, Japan
Published online on: July 25, 2012 https://doi.org/10.3892/or.2012.1935
Pages: 1269-1274

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Abstract

The present study investigates whether the expression levels of heat shock protein 27 (HSP27) in colon cancer cells are associated with 5-fluorouracil (5-FU) sensitivity in a xenograft model, as well as the mechanism responsible for regulating 5-FU sensitivity. HCT116 cells which have a high expression of HSP27 were stably transfected with specific short hairpin RNA (shRNA) in order to suppress HSP27 expression. The association between HSP27 protein expression levels and 5-FU sensitivity was evaluated in a mouse xenograft model. The mRNA expression of 5-FU metabolic enzymes and cell apoptosis were also analyzed in the transfected cells. The suppression of HSP27 protein expression led to enhanced 5-FU sensitivity. The mRNA expression levels of dihydropyrimidine dehydrogenase and orotate phosphoribosyltransferase, but not those of thymidylate synthase, and the number of apoptotic cells increased in the transfected cells after 5-FU exposure. In conclusion, the suppression of HSP27 expression in colon cancer cells may promote 5-FU sensitivity by inducing apoptosis, despite the acceleration in 5-FU metabolism.

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