Howe Louise R, Subbaramaiah Kotha, Patel Jay, Masferrer Jaime L, Deora Aparna, Hudis Clifford, Thaler Howard T, Muller William J, Du Baoheng, Brown Anthony M C, Dannenberg Andrew J
Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, New York 10021, USA.
Cancer Res. 2002 Oct 1;62(19):5405-7.
Cyclooxygenase 2 (HER-2) (Cox-2), an inducible form of Cox, is overexpressed in HER-2/neu-positive human breast cancers. The aim of this study was to determine whether celecoxib, a selective Cox-2 inhibitor, protected against HER-2/neu-induced experimental breast cancer. Cox-2 protein was detected in breast carcinomas from mouse mammary tumor virus (MMTV)/neu mice. Treatment with celecoxib (500 ppm) significantly reduced the incidence of mammary tumors in MMTV/neu mice (P = 0.003) and caused about a 50% reduction in mammary prostaglandin E2 (PGE2) levels. Because mammary glands from MMTV/neu mice expressed all four PGE2 receptor subtypes, we speculate that signaling through PGE2 receptors is important for mammary tumorigenesis. These results strengthen the rationale for developing clinical trials to determine whether selective Cox-2 inhibitors possess anticancer properties in humans at risk for breast cancer.
环氧化酶2（HER-2）（Cox-2）是Cox的一种诱导型形式，在HER-2/neu阳性的人类乳腺癌中过度表达。本研究的目的是确定选择性Cox-2抑制剂塞来昔布是否能预防HER-2/neu诱导的实验性乳腺癌。在小鼠乳腺肿瘤病毒（MMTV）/neu小鼠的乳腺癌中检测到Cox-2蛋白。用塞来昔布（500 ppm）治疗可显著降低MMTV/neu小鼠乳腺肿瘤的发生率（P = 0.003），并使乳腺前列腺素E2（PGE2）水平降低约50%。由于MMTV/neu小鼠的乳腺表达所有四种PGE2受体亚型，我们推测通过PGE2受体的信号传导对乳腺肿瘤发生很重要。这些结果为开展临床试验以确定选择性Cox-2抑制剂在有乳腺癌风险的人类中是否具有抗癌特性提供了理论依据。
