title: Acetylsalicylic Acid Exhibits Antitumor Effects in Esophageal Adenocarcinoma Cells In Vitro and In Vivo.
abstract: Recent observational studies have shown therapeutic benefits of acetylsalicylic acid (ASA) in several types of cancer. We examined whether ASA exerts antitumor activity in esophageal adenocarcinoma (EAC).
  
  
  
  Human EAC cells (OE33) were treated with ASA (0-5 mM) to evaluate proliferation, apoptosis, and migration. In vivo model: OE33-derived tumors were subcutaneously implanted into athymic mice which were allocated to ASA (5 or 50 mg/kg/day)/vehicle (5-6 animals/group). Tumor growth was assessed every 2-3 days, and after 40 days, mice were euthanized. Plasma drug levels were determined by high-performance liquid chromatography. Histological and immunohistochemical (Ki67, activated caspase-3) analysis of tumors were performed. The effect of ASA on tumor prostaglandin E2 (PGE2) levels was also evaluated.
  
  
  
  In vitro cell proliferation and migration were significantly inhibited while apoptosis increased (p < 0.05) by ASA. Although ASA did not induce tumor remission, tumor progression was significantly lower in ASA-treated mice when compared to non-treated animals (478 % in mice treated with 5 mg/kg/day ASA vs. 2696 % control; 748 % in mice treated with 50 mg/kg/day ASA vs. 2670 % control). Maximum tumor inhibition was 92 and 85 %, respectively. This effect was associated with a significant decrease of proliferation index in tumors. ASA 5 mg/kg/day did not modify tumor PGE2 levels. Whereas tumor PGE2 content in mice treated with ASA 50 mg/kg was lower than in control mice, the difference was not significant.
  
  
  
  Although these results need to be confirmed in other EAC cells, our data suggest a role for ASA in the treatment of this tumor.
authors.affiliation: IIS Aragón, Saragossa, Spain. epiazor@unizar.es.|Instituto Aragonés de Ciencias de la Salud, Centro de Investigación Biomédica de Aragón, Avda. San Juan Bosco, 13, 50009, Saragossa, Spain. epiazor@unizar.es.|CIBER Enfermedades Hepáticas y digestivas (CIBERehd), Saragossa, Spain. epiazor@unizar.es.
authors.forename: Elena
authors.identifier: 0000-0001-5813-3445
authors.initials: E
authors.lastname: Piazuelo
authors.affiliation: CIBER Enfermedades Hepáticas y digestivas (CIBERehd), Saragossa, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Esquivias
authors.affiliation: Instituto Aragonés de Ciencias de la Salud, Centro de Investigación Biomédica de Aragón, Avda. San Juan Bosco, 13, 50009, Saragossa, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: De Martino
authors.affiliation: Service of Pathology, University Hospital Lozano Blesa, Saragossa, Spain.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Cebrián
authors.affiliation: University of Zaragoza, Saragossa, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Conde
authors.affiliation: University of Zaragoza, Saragossa, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Santander
authors.affiliation: University of Zaragoza, Saragossa, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Emperador
authors.affiliation: IIS Aragón, Saragossa, Spain.|Instituto Aragonés de Ciencias de la Salud, Centro de Investigación Biomédica de Aragón, Avda. San Juan Bosco, 13, 50009, Saragossa, Spain.|CIBER Enfermedades Hepáticas y digestivas (CIBERehd), Saragossa, Spain.
authors.forename: María Asunción
authors.initials: MA
authors.lastname: García-González
authors.affiliation: University of Zaragoza, Saragossa, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Carrera-Lasfuentes
authors.affiliation: IIS Aragón, Saragossa, Spain.|CIBER Enfermedades Hepáticas y digestivas (CIBERehd), Saragossa, Spain.|University of Zaragoza, Saragossa, Spain.|Service of Gastroenterology, University Hospital Lozano Blesa, Saragossa, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Lanas
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000494:pharmacology*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone / Q000378:metabolism; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D019394:Ki-67 Antigen / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019394:Ki-67 Antigen; D053148:Caspase 3; D015232:Dinoprostone; D001241:Aspirin
keywords: Acetylsalicylic acid; Aspirin; Cyclooxygenase; Esophageal adenocarcinoma; Prostaglandin E2; Xenografts