Cyclooxygenase inhibitors decrease the growth and induce regression of human esophageal adenocarcinoma xenografts in nude mice

  • Authors:
    • Sonia Santander
    • Carmelo Cebrián
    • Paula Esquivias
    • Blanca Conde
    • Francisco Esteva
    • Pilar Jiménez
    • Javier Ortego
    • Ángel Lanas
    • Elena Piazuelo
  • View Affiliations

  • Published online on: October 3, 2011     https://doi.org/10.3892/ijo.2011.1219
  • Pages: 527-534
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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.

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February 2012
Volume 40 Issue 2

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APA
Santander, S., Cebrián, C., Esquivias, P., Conde, B., Esteva, F., Jiménez, P. ... Piazuelo, E. (2012). Cyclooxygenase inhibitors decrease the growth and induce regression of human esophageal adenocarcinoma xenografts in nude mice. International Journal of Oncology, 40, 527-534. https://doi.org/10.3892/ijo.2011.1219
MLA
Santander, S., Cebrián, C., Esquivias, P., Conde, B., Esteva, F., Jiménez, P., Ortego, J., Lanas, Á., Piazuelo, E."Cyclooxygenase inhibitors decrease the growth and induce regression of human esophageal adenocarcinoma xenografts in nude mice". International Journal of Oncology 40.2 (2012): 527-534.
Chicago
Santander, S., Cebrián, C., Esquivias, P., Conde, B., Esteva, F., Jiménez, P., Ortego, J., Lanas, Á., Piazuelo, E."Cyclooxygenase inhibitors decrease the growth and induce regression of human esophageal adenocarcinoma xenografts in nude mice". International Journal of Oncology 40, no. 2 (2012): 527-534. https://doi.org/10.3892/ijo.2011.1219