title: The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cells.
abstract: BACKGROUND
  Acetylsalicylic acid (ASA, aspirin), the most common nonsteroidal anti-inflammatory drug (NSAID), has been shown to have a protective effect against the incidence and mortality of colorectal cancer. However, the mechanism of its anticancer function remains unclear. The aim of this study was to determine the effects of acetylsalicylic acid on proliferation, apoptosis, and invasion in human cyclooxygenase-2 (COX-2) negative colorectal cancer cell lines.
  
  
  METHODS
  After treatment with various concentrations of ASA, cell proliferation was measured in the human colon cancer cell line SW480. Apoptotic cells were identified by transmission electron microscopy, acridine orange staining, and flow cytometry. The invasive potential of SW480 cells was detected using an in vitro invasion assay. The production of carcinoembryonic antigen was measured by microparticle enzyme immunoassay. Expression of Bcl2, Bax, CD44v6, and nm23 were evaluated by immunocytochemistry.
  
  
  RESULTS
  ASA significantly inhibited the proliferation of SW480 cells and stimulated apoptosis. Production of carcinoembryonic antigen and the invasive potential of SW480 cells were also inhibited by ASA. After treatment with ASA, down-regulation of Bcl2 and CD44v6 expression and up-regulation of nm23 expression were observed in SW480 cells. No obvious effect of ASA was found on Bax expression.
  
  
  CONCLUSIONS
  Our findings reveal that ASA inhibits the proliferation and promotes apoptosis in the human colon cancer cell line SW480. Down-regulation of Bcl2 expression might represent a potential mechanism by which ASA induces apoptosis in this COX-2 negative colon cancer cell line. Our results also suggest that ASA decreases the invasive potential of these colon cancer cells. Decreased CEA content and CD44v6 expression and elevated nm23 expression may contribute to the effect of ASA on invasive potential of SW480 colon cancer cells.
authors.affiliation: Department of Gastroenterology, RenMin Hospital of Wuhan University, Wuhan, China, Ruhr-University Bochum, Bochum, Germany.
authors.forename: H-G
authors.initials: HG
authors.lastname: Yu
authors.forename: J-A
authors.initials: JA
authors.lastname: Huang
authors.forename: Y-N
authors.initials: YN
authors.lastname: Yang
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.forename: H-S
authors.initials: HS
authors.lastname: Luo
authors.forename: J-P
authors.initials: JP
authors.lastname: Yu
authors.forename: J J
authors.initials: JJ
authors.lastname: Meier
authors.forename: H
authors.initials: H
authors.lastname: Schrader
authors.forename: A
authors.initials: A
authors.lastname: Bastian
authors.forename: W E
authors.initials: WE
authors.lastname: Schmidt
authors.forename: F
authors.initials: F
authors.lastname: Schmitz
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000648:ultrastructure; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D019940:Genes, bcl-1; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007527:Isoenzymes; D008565:Membrane Proteins; D008854:Microscopy, Electron; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D011451:Prostaglandin-Endoperoxide Synthases; D014157:Transcription Factors / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C112697:CD44v6 antigen; D002272:Carcinoembryonic Antigen; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D008565:Membrane Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins; D001241:Aspirin