Celecoxib inhibits invasion and metastasis via a cyclooxygenase 2-independent mechanism in an in vitro model of Ewing sarcoma
Celecoxib inhibits invasion and metastasis via a cyclooxygenase 2-independent mechanism in an in vitro model of Ewing sarcoma
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DOI：
10.1016/j.jpedsurg.2012.03.031
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发表时间：
2012-06-01
影响因子：
2.4
通讯作者：
Soffer, Samuel Z.
中科院分区：
文献类型：
--
作者：
Barlow, Meade;Edelman, Morris;Soffer, Samuel Z.
背景/介绍：以前，我们报道了塞来昔布，一种环氧合酶-2（考克斯-2）抑制剂，在尤文肉瘤模型中预防肺转移，但不影响肿瘤生长。环氧合酶-2抑制已被提议作为抗转移策略。方法：尤文肉瘤细胞悬浮在可溶性基底膜提取物（Cultrex; Trevigen，Inc，盖瑟斯堡，MD），并补充塞来昔布或罗非昔布，第二个考克斯-2抑制剂，以上过滤器。对照接受溶剂。48小时后，对侵入基底膜和滤膜的细胞进行染色和计数。结果：与对照组相比，塞来昔布组的侵袭能力明显降低，且与对照组相比，塞来昔布组的侵袭能力明显降低。加入PGE（2）不能克服塞来昔布的抑制作用。与对照组相比，罗非昔布对尤文肉瘤细胞的侵袭能力无明显影响，无论是否加用PGE（2）。前列腺素E-2（考克斯-2的下游产物）在体外没有逆转抑制作用，表明塞来昔布通过考克斯-2非依赖性机制发挥作用。尽管罗非考昔更有选择性地抑制考克斯-2，但它不能抑制侵袭，这进一步支持了上述观点。(C)2012 Elsevier Inc. All rights reserved.
Background/Introduction: Previously, we reported that celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, prevented lung metastases but did not affect tumor growth in a model of Ewing sarcoma. Cyclooxygenase-2 inhibition has been proposed as an antimetastatic strategy. The mechanism of action remains unclear.Methods: Ewing sarcoma cells were suspended in a soluble basement membrane extract (Cultrex; Trevigen, Inc, Gaithersburg, MD) and supplemented with celecoxib or with rofecoxib, a second COX-2 inhibitor, above a filter. Controls received solvent. After 48 hours, the cells that invaded through the basement membrane and filter were stained and counted. The assay was repeated with the addition of 500-nM prostaglandin E2 (PGE(2)).Results: Invasion was significantly decreased in the celecoxib groups compared with the control. The addition of PGE(2) did not overcome celecoxib inhibition. Rofecoxib did not significantly affect invasion compared with control either with or without PGE(2).Conclusions: Celecoxib significantly inhibits invasion of Ewing sarcoma cells in vitro. Prostaglandin E-2, a downstream product of COX-2, did not reverse in vitro inhibition, suggesting that celecoxib acts through a COX-2-independent mechanism. This is further supported by the failure of rofecoxib to inhibit invasion despite more selectively inhibiting COX-2. (C) 2012 Elsevier Inc. All rights reserved.