title: Suppression of heat shock protein 27 expression promotes 5-fluorouracil             sensitivity in colon cancer cells in a xenograft model.
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.
authors: Department of Surgery, School of Medicine, Keio University, Tokyo                     160-8582, Japan.
authors: Ryohei
authors: R
authors: Hayashi
authors: Yoshiyuki
authors: Y
authors: Ishii
authors: Hiroki
authors: H
authors: Ochiai
authors: Atsushi
authors: A
authors: Matsunaga
authors: Takashi
authors: T
authors: Endo
authors: Hirotoshi
authors: H
authors: Hasegawa
authors: Yuko
authors: Y
authors: Kitagawa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018832:Molecular Chaperones; D009962:Orotate Phosphoribosyltransferase / Q000235:genetics; D034741:RNA, Small Interfering; D013940:Thymidylate Synthase / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D034741:RNA, Small Interfering; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D005472:Fluorouracil