Cyclooxygenase-1 is overexpressed and promotes angiogenic growth factor production in ovarian cancer.
Cyclooxygenase-1 is overexpressed and promotes angiogenic growth factor production in ovarian cancer.
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发表时间：
2003-03
期刊：
影响因子：
11.2
通讯作者：
Rajnish A. Gupta;Lovella Tejada;Beverly J. Tong;S. Das;J. Morrow;S. Dey;R. Dubois
中科院分区：
文献类型：
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作者：
Rajnish A. Gupta;Lovella Tejada;Beverly J. Tong;S. Das;J. Morrow;S. Dey;R. Dubois
抑制环氧合酶-2(COX-2)的催化活性已被证明在体内成功地限制了上皮源性肿瘤的生长。COX-2抑制剂治疗在预防和/或治疗卵巢癌方面是否有益，目前尚不清楚。卵巢癌是世界上最致命的妇科恶性肿瘤。大多数卵巢癌患者接受细胞减灭术。由于许多用于治疗卵巢癌的细胞毒性药物都会诱导COX-2的表达，因此我们从未接受过细胞减量治疗的患者样本中专门选择了COX亚型的表达分析。与正常卵巢组织相比，大多数卵巢组织中COX-1的表达水平升高，而不是COX-2、mRNA和蛋白的表达。肿瘤内高表达COX-1的病灶区域也有高水平的促血管生成蛋白。选择性抑制COX-1，而不是COX-2，可抑制花生四烯酸刺激的血管内皮生长因子的产生，这种抑制可被前列腺素E(2)逆转。因此，COX-1可能通过刺激新生血管而促进卵巢癌的发展。检验COX抑制作为卵巢癌辅助治疗有效性的临床研究可能会发现，与COX-2选择性药物相比，使用COX-1选择性或非选择性环氧合酶抑制剂辅助治疗卵巢癌可能会有更好的效果。
Inhibition of cyclooygenase-2 (COX-2) catalytic activity has proven successful in restricting the growth of epithelial-derived cancers in vivo. Whether COX-2 inhibitor therapy would be beneficial in the prevention and/or treatment of ovarian cancer, the most lethal gynecological malignancy worldwide, is not known. Most patients with ovarian cancer undergo cytoreductive therapy. Because many of the cytotoxic drugs used to treat ovarian cancer induce COX-2 expression, samples from patients that had not undergone cytoreductive therapy were specifically chosen for COX isoform expression analysis. A majority of specimens exhibited elevated levels of COX-1, not COX-2, mRNA, and protein compared with normal ovarian tissue. Focal regions within the tumor expressing high COX-1 also had elevated levels of pro-angiogenic proteins. Selective inhibition of COX-1, not COX-2, inhibited arachidonic acid-stimulated vascular endothelial growth factor production, which could be reversed by cotreatment with prostaglandin E(2). Thus, COX-1 may contribute to carcinoma development in the ovary through stimulation of neovascularization. Clinical studies testing the efficacy of COX inhibition as adjuvant therapy for ovarian cancer may see more beneficial effects with adjuvant therapy with either a COX-1 selective or nonselective cyclooxygenase inhibitor as compared with a COX-2 selective drug.