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

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1269-1274
Number of pages6
JournalOncology reports
Volume28
Issue number4
DOIs
Publication statusPublished - 2012 Oct 1

    Fingerprint

Keywords

  • 5-fluorouracil
  • Colon cancer
  • Heat shock protein 27
  • Xenograft model

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this