Elevated cyclooxygenase-2 (COX-2) closely associates with tumor progression and distant metastasis in various human cancers. However, the role of COX-2 in epithelial ovarian cancer (EOC), and its mechanistic details, remain poorly understood. In the present study, we tested hypothesis that COX-2 induces loss of expression of E-cadherin, with resulting promotion of cancer cells' invasiveness in ovarian cancer. First, we observed an inverse relationship between COX-2 and E-cadherin expression as COX-2 was enhanced but E-cadherin was decreased in surgically-resected specimens of EOC. Depletion of COX-2, by celecoxib treatment, resulted in attenuated nuclear translocation of Snail, and, in turn, significantly increased E-cadherin in EOC cell line SKOV3, which was established to be due to the reduced binding of Snail onto E-cadherin promoter. Such COX-2 inhibition resulted in reduced invasion of EOC cells, similar to what was achieved through Snail silencing in SKOV as well as ES-2 EOC cells. These results suggest that COX-2-Snail signaling plays a critical role in regulation of E-cadherin and might provide insights into mechanisms for paracrine inflammation-mediated aggressiveness in EOC.

升高的环氧合酶2（COX-2）与各种人类癌症中的肿瘤进展和远处转移密切相关。然而，对COX-2在上皮性卵巢癌（EOC）中的作用及其机理细节仍知之甚少。在本研究中，我们测试了以下假设：COX-2诱导E-钙黏着蛋白表达的丧失，从而促进卵巢癌细胞中癌细胞的侵袭性。首先，我们观察到在手术切除的EOC标本中，COX-2增强但E-钙粘蛋白减少，因此COX-2与E-钙粘蛋白表达呈反比关系。通过塞来昔布处理使COX-2耗竭，导致Snail的核转运减弱，进而显着增加EOC细胞系SKOV3中的E-钙粘蛋白，这是由于Snail与E-钙粘蛋白的结合减少所致启动子。这种COX-2抑制作用导致EOC细胞的侵袭减少，这与通过SKOV的Snail沉默以及ES-2 EOC细胞实现的抑制作用相似。这些结果表明，COX-2-Snail信号传导在E-钙粘蛋白的调节中起着关键作用，并可能为EOC中旁分泌炎症介导的侵袭性机制提供见解。