Elena Piazuelo1,2,3, Paula Esquivias4, Alba De Martino5, Carmelo Cebrián6, Blanca Conde7, Sonia Santander7, Sonia Emperador7, María Asunción García-González8,5,4, Patricia Carrera-Lasfuentes7, Angel Lanas8,4,7,9. 1. IIS Aragón, Saragossa, Spain. epiazor@unizar.es. 2. Instituto Aragonés de Ciencias de la Salud, Centro de Investigación Biomédica de Aragón, Avda. San Juan Bosco, 13, 50009, Saragossa, Spain. epiazor@unizar.es. 3. CIBER Enfermedades Hepáticas y digestivas (CIBERehd), Saragossa, Spain. epiazor@unizar.es. 4. CIBER Enfermedades Hepáticas y digestivas (CIBERehd), Saragossa, Spain. 5. Instituto Aragonés de Ciencias de la Salud, Centro de Investigación Biomédica de Aragón, Avda. San Juan Bosco, 13, 50009, Saragossa, Spain. 6. Service of Pathology, University Hospital Lozano Blesa, Saragossa, Spain. 7. University of Zaragoza, Saragossa, Spain. 8. IIS Aragón, Saragossa, Spain. 9. Service of Gastroenterology, University Hospital Lozano Blesa, Saragossa, Spain.
Abstract
BACKGROUND AND AIM: 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). METHODS: 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. RESULTS: 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. CONCLUSION: Although these results need to be confirmed in other EAC cells, our data suggest a role for ASA in the treatment of this tumor.
BACKGROUND AND AIM: 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). METHODS: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 tumorprostaglandin E2 (PGE2) levels was also evaluated. RESULTS: 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 tumorPGE2 levels. Whereas tumorPGE2 content in mice treated with ASA 50 mg/kg was lower than in control mice, the difference was not significant. CONCLUSION: Although these results need to be confirmed in other EAC cells, our data suggest a role for ASA in the treatment of this tumor.
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