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

Oncol Rep. 2012 Oct;28(4):1269-74. doi: 10.3892/or.2012.1935. Epub 2012 Jul 25.

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.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Dihydrouracil Dehydrogenase (NADP) / genetics
  • Female
  • Fluorouracil / pharmacokinetics
  • Fluorouracil / pharmacology*
  • Gene Expression Regulation, Enzymologic / drug effects
  • HSP27 Heat-Shock Proteins / genetics*
  • HSP27 Heat-Shock Proteins / metabolism
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Orotate Phosphoribosyltransferase / genetics
  • RNA, Small Interfering
  • Thymidylate Synthase / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • HSP27 Heat-Shock Proteins
  • HSPB1 protein, human
  • RNA, Small Interfering
  • Dihydrouracil Dehydrogenase (NADP)
  • Thymidylate Synthase
  • Orotate Phosphoribosyltransferase
  • Fluorouracil