Cyclooxygenase 2 mediates the antiangiogenic effect of rapamycin in Ewing sarcoma.

Abstract:

BACKGROUND:Rapamycin can inhibit tumor growth and angiogenesis in various human cancers. Cyclooxygenase 2 (COX-2) is involved in the angiogenic process. We hypothesized that the antiangiogenic effect of rapamycin may be mediated by suppression of COX-2. METHODS:Ewing sarcoma (ES) cells were implanted in athymic mice. Selected animals were treated with rapamycin for 5 weeks. Tumor vascularity was assessed by lectin perfusion angiography and immunohistochemistry. Phosphorylation of mammalian target of rapamycin pathway proteins was determined by Western blot analysis. Staining of COX-2 protein was determined by immunohistochemistry, and expression of COX-2 messenger RNA levels was assessed with quantitative real-time (RT) polymerase chain reaction. RESULTS:Mean tumor weights were significantly reduced in the treated group (5.43 g +/- 1.43 SEM vs 0.49 g +/- 0.15 SEM, P < .003). There was abundant vasculature in the control group and blunted vascularity in the treated xenografts. The phosphorylation of p70s6k and Akt was not inhibited in the rapamycin-treated tumors. Cyclooxygenase 2 was suppressed in the treated xenografts at both the protein and messenger RNA levels. CONCLUSION:Low-dose rapamycin inhibits tumor growth and angiogenesis in human ES without inhibiting the phosphorylation of p70s6k and Akt. Cyclooxygenase 2 levels are inhibited by low-dose treatment of ES with rapamycin. Cyclooxygenase 2 suppression may mediate the antiangiogenic effect of rapamycin in Ewing sarcoma.

journal_name

J Pediatr Surg

authors

Lipskar AM,Glick RD,Huang J,Fisher JC,DeVoti J,Pica R,Edelman M,Steinberg BM,Soffer SZ

doi

10.1016/j.jpedsurg.2009.02.037

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

1139-46; discussion 1146-7

issue

6

eissn

0022-3468

issn

1531-5037

pii

S0022-3468(09)00168-7

journal_volume

44

pub_type

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