COX-2 correlates with F-box protein, Skp2 expression and prognosis in human gastric carcinoma.
COX-2 correlates with F-box protein, Skp2 expression and prognosis in human gastric carcinoma.
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DOI：
10.3892/ijo.26.2.353
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发表时间：
2005-02
影响因子：
5.2
通讯作者：
S. Honjo;S. Kase;M. Osaki;T. Ardyanto;N. Kaibara;Hisao Ito
中科院分区：
文献类型：
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作者：
S. Honjo;S. Kase;M. Osaki;T. Ardyanto;N. Kaibara;Hisao Ito
环氧化酶（考克斯）-2的表达受生长因子、肿瘤促进因子和细胞因子的诱导，与肿瘤的发生、发展和细胞凋亡的抑制有关。为了阐明考克斯-2的病理学意义，我们检测了选择性考克斯-2抑制剂NS 398对两种人胃癌细胞系MKN-45和KATO-III的影响，以及Skp 2、P27/Kip 1和考克斯-2蛋白在人胃癌中的表达。NS 398以时间和剂量依赖性方式抑制细胞生长，并在MKN-45中将细胞周期阻滞在G 0/G1期而不诱导凋亡，但在KATO-III中没有影响。在MKN-45中，NS 398诱导P27/Kip 1上调，考克斯-2、cyclin D1和Skp 2下调。63例手术切除胃癌的免疫组化结果显示，考克斯-2表达与Skp 2表达相关，P27/Kip 1表达与考克斯-2和Skp 2表达呈负相关。高水平的考克斯-2或Skp 2与低生存率显著相关（P=0.02和P=0.004）。我们的研究结果表明：在表达考克斯-2的胃癌细胞中，NS 398通过细胞周期阻滞诱导细胞增殖抑制，并抑制Skp 2的表达，和B）考克斯-2有助于Skp 2的表达和人胃癌中的低存活率。
The expression of cyclooxygenase (COX)-2 is induced by growth factors, tumor promoters and cytokines, and is correlated with carcinogenesis, tumor progression and inhibition of apoptosis. To clarify the pathological significance of COX-2, we examined the effect of a selective COX-2 inhibitor, NS398, on two human gastric carcinoma cell lines, MKN-45 and KATO-III, and the expression of Skp2, P27/Kip1 and COX-2 protein in human gastric carcinomas. NS398 inhibited cell growth in a time- and dose-dependent manner and exerted cell cycle arrest in the G0/G1 phase without induction of apoptosis in MKN-45, but had no effect in KATO-III. In MKN-45, NS398 induced up-regulation of P27/Kip1 and down-regulation of COX-2, cyclin D1 and Skp2. Immunohistochemistry using 63 surgically resected gastric carcinomas disclosed that COX-2 expression was correlated with Skp2 expression and that P27/Kip1 expression was inversely correlated with COX-2 and Skp2 expression. High levels of COX-2 or Skp2 were significantly correlated with poor survival (P=0.02 and P=0.004). Our results suggested that: a) NS398 induced inhibition of cell proliferation through cell cycle arrest and suppressed the expression of Skp2 in COX-2-expressing gastric carcinoma cells, and b) COX-2 contributes to the expression of Skp2 and poor survival in human gastric carcinomas.