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

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.

journal_name

J Pediatr Surg

journal_title

Journal of pediatric surgery

authors

Gendy AS,Lipskar A,Glick RD,Steinberg BM,Edelman M,Soffer SZ

doi

10.1016/j.jpedsurg.2010.09.074

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

108-14

issue

1

eissn

0022-3468

issn

1531-5037

pii

S0022-3468(10)00895-X

journal_volume

46

pub_type

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