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J Pediatr Surg. 2011 Jan;46(1):108-14. doi: 10.1016/j.jpedsurg.2010.09.074.

Selective inhibition of cyclooxygenase-2 suppresses metastatic disease without affecting primary tumor growth in a murine model of Ewing sarcoma.

Author information

1
Division of Pediatric Surgery, Steven and Alexandra Cohen Children's Medical Center of New York, North Shore-Long Island Jewish Health System, New Hyde Park, NY 11040, USA.

Abstract

BACKGROUND/PURPOSE:

Mammalian target of rapamycin suppression by rapamycin inhibits tumor growth and neovascularization via cyclooxygenase-2 (COX-2) downregulation with no effect on lung metastases. We hypothesize that combining a selective COX-2 antagonist (celecoxib) with rapamycin would decrease lung metastases.

METHODS:

Ewing sarcoma cells (SK-NEP-1) were surgically implanted into the left kidney of athymic mice (n = 40). The mice were divided into 4 treatment groups (control, rapamycin only, celecoxib only, and combination) and then killed at 6 weeks. Primary tumors were weighed. Vasculature was examined using lectin angiography and immunohistochemistry, and lung metastases were examined using H&E and CD99 immunostaining. Tumor weight and lung metastases were analyzed.

RESULTS:

Mean primary tumor weights were significantly reduced in the rapamycin-treated groups but not in the celecoxib-only group. Lectin angiography and endothelial markers immunostaining showed markedly decreased vascularity in the rapamycin-treated groups but not in the celecoxib-only group. Celecoxib-treated groups showed significantly fewer mice with lung metastases than non-celecoxib-treated groups.

CONCLUSION:

Celecoxib prevents lung metastasis in a murine model of Ewing sarcoma with no effect on tumor size or neovascularization. Cyclooxygenase-2 may represent a future potential target for metastatic disease prevention.

PMID:
21238650
DOI:
10.1016/j.jpedsurg.2010.09.074
[Indexed for MEDLINE]

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