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Updated: May 28, 2026
Subculture and Cryopreservation of Esophageal Adenocarcinoma Organoids: Pros and Cons for Single Cell Digestion
Published on: July 6, 2022
Cyclooxygenase inhibitors decrease the growth and induce regression of human esophageal adenocarcinoma
Sonia Santander1, Carmelo Cebrián, Paula Esquivias
1Aragon Health Research Institute (IIS Aragon), University of Zaragoza School of Medicine, Department of Pharmacology and Physiology, C/Domingo Miral s/n, 50009 Zaragoza, Spain. soniasb@gmail.com
Abstract:
Cyclooxygenase (COX) inhibition has been shown to prevent the development of esophageal adenocarcinoma (EAC). However, the potential of this approach for treatment of established cancer has been poorly investigated. Our objective was to determine whether non-selective or selective inhibition of the COX pathway affects the growth of esophageal adenocarcinoma xenografts in nude mice. A human esophageal adenocarcinoma xenograft model was established by subcutaneous inoculation of OE33 cells in nude mice. Small tumor slices harvested from four OE33 xenografts were implanted in the flanks of new mice that were randomized to different treatments (6 animals per group): indomethacin (3 mg/kg/day), parecoxib (0.11 and 0.22 mg/kg/day) or a selective prostaglandin E₂ receptor antagonist (AH-23848B, 1 mg/kg/day). For each treatment, a control group of 6 animals (vehicle) carrying xenografts from the same OE33 tumor was included. Tumor growth was measured twice a week. After 8 weeks mice were euthanized. Tumors were assessed by histological analysis, mRNA expression of COX isoenzymes, PGE₂ receptors and PGE₂ content. All OE33 tumors were poorly differentiated esophageal adenocarcinomas. Tumors expressed COX-2, EP₁, EP₂ and EP₄ receptor mRNA. Treatment with parecoxib, higher dose or indomethacin significantly inhibited tumor growth. Furthermore, indomethacin induced tumor regression (74 vs 582% in control animals; p<0.01). However, AH-23848B or parecoxib low dose failed to affect tumor growth significantly. PGE₂ content in tumors was significantly decreased by high-dose parecoxib and indomethacin. Indomethacin and parecoxib inhibit the growth of human esophageal adenocarcinoma xenografts in nude mice, which suggests a potential role for NSAIDs or selective COX-2 inhibitors for EAC chemotherapy.
Insights
Non-selective cyclooxygenase (COX) inhibition with indomethacin and selective COX-2 inhibition with parecoxib significantly inhibited esophageal adenocarcinoma xenograft growth in mice. Indomethacin even induced tumor regression, suggesting NSAIDs and COX-2 inhibitors may aid EAC chemotherapy.
Area of Science:
- Oncology
- Pharmacology
- Gastroenterology
Background:
- Cyclooxygenase (COX) inhibition is known to prevent esophageal adenocarcinoma (EAC) development.
- The efficacy of COX inhibition for treating established EAC remains largely unexplored.
Purpose of the Study:
- To investigate the effect of non-selective and selective COX inhibition on the growth of established esophageal adenocarcinoma xenografts in mice.
- To evaluate the therapeutic potential of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors in EAC.
Main Methods:
- A human esophageal adenocarcinoma xenograft model using OE33 cells in nude mice was established.
- Mice bearing xenografts were treated with indomethacin (non-selective COX inhibitor), parecoxib (selective COX-2 inhibitor), or AH-23848B (selective prostaglandin E₂ receptor antagonist).
- Tumor growth, histology, mRNA expression of COX isoenzymes and PGE₂ receptors, and PGE₂ content were assessed.
Main Results:
- Indomethacin and high-dose parecoxib significantly inhibited tumor growth.
- Indomethacin treatment led to significant tumor regression (74% reduction compared to controls).
- PGE₂ content was significantly reduced by high-dose parecoxib and indomethacin, while AH-23848B and low-dose parecoxib showed no significant effect.
Conclusions:
- Indomethacin and parecoxib demonstrate inhibitory effects on human esophageal adenocarcinoma xenograft growth in vivo.
- These findings suggest a potential therapeutic role for NSAIDs and selective COX-2 inhibitors in the chemotherapy of esophageal adenocarcinoma.
