title: Extracellular chaperonin 10 augments apoptotic cell death induced by 5-fluorouracil in human colon cancer cells.
abstract: OBJECTIVE
  The molecular mechanisms involved in resistance to 5-fluorouracil (5-FU) in colon cancer patients remain to be elucidated. The purpose of this study was to identify proteins associated with 5-FU resistance in colon cancer.
  
  
  METHODS
  Proteins secreted from a 5-FU-resistant human colon cancer cell line (SNU-C4 5-FU 200) were analyzed by two-dimensional gel electrophoresis-based proteomics, and identified using matrix-associated laser desorption/ionization-mass spectroscopy analysis and SWISS-PROT database searches. The expression levels of candidate proteins were determined by Western blotting and cell proliferation was monitored by MTT assay.
  
  
  RESULTS
  Chaperonin 10 (cpn10) was secreted at a lower level by 5-FU-resistant cells compared to the non-resistant parent cell line. The proliferation of both the parent and 5-FU-resistant cell lines increased slightly when extracellular cpn10 alone was added. However, in the presence of 5-FU, cpn10 augmented 5-FU-induced apoptotic death in both cell lines. Cpn10 led to activation of extracellular signal-regulated kinase 1/2 (ERK 1/2), and a specific ERK 1/2 inhibitor, PD98059, completely inhibited cpn10-stimulated cell proliferation.
  
  
  CONCLUSIONS
  Our findings indicate that concurrent treatment with cpn10 and 5-FU warrants further investigation in an effort to overcome 5-FU resistance and enhance the efficacy of 5-FU therapy for colon cancer.
authors: Kun
authors: K
authors: Kim
authors: Seung-Gu
authors: SG
authors: Yeo
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018835:Chaperonin 10 / Q000378:metabolism* / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D015180:Electrophoresis, Gel, Two-Dimensional; D005419:Flavonoids / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009363:Neoplasm Proteins / Q000032:analysis*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000964:Antimetabolites, Antineoplastic; D018835:Chaperonin 10; D005419:Flavonoids; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D005472:Fluorouracil