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Acetylsalicylic Acid Exhibits Antitumor Effects in Esophageal Adenocarcinoma Cells In Vitro and In Vivo

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.

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Abbreviations

ASA:

Acetyl salicylic acid

SA:

Salicylic acid

EAC:

Esophageal adenocarcinoma

GERD:

Gastroesophageal reflux disease

NSAIDs:

Nonsteroidal anti-inflammatory drugs

COX:

Cyclooxygenase

TI:

Tumor inhibition

R t :

Tumor remission

PGE2 :

Prostaglandin E2

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Authors’ contribution

Piazuelo E designed the study and wrote the manuscript; Esquivias P performed all biochemical analysis, contributed to animal and in vitro experiments, and to the edition of the manuscript. De Martino A and Cebrián C performed histological and immunohistochemical analysis; Conde B and Emperador S were involved in the experiments in nude mice. Santander S performed in vitro studies; García-González MA was involved in all biochemical determinations and provided vital reagents and analytical tools; Carreras P and Lanas A were involved in the design of the study, statistical analysis, and editing the manuscript.

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Correspondence to Elena Piazuelo.

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Conflict of interest

AL is advisor to Bayer and has received an investigator initiated grant from Bayer for investigations unrelated to this study. The rest of authors declared that they have no competing interests.

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Piazuelo, E., Esquivias, P., De Martino, A. et al. Acetylsalicylic Acid Exhibits Antitumor Effects in Esophageal Adenocarcinoma Cells In Vitro and In Vivo. Dig Dis Sci 61, 2896–2907 (2016). https://doi.org/10.1007/s10620-016-4225-z

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Keywords

  • Esophageal adenocarcinoma
  • Acetylsalicylic acid
  • Aspirin
  • Cyclooxygenase
  • Prostaglandin E2
  • Xenografts