Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522
Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522
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DOI：
10.1038/sj.bjc.6694262
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发表时间：
1999-12-01
影响因子：
8.8
通讯作者：
Muto, T
中科院分区：
文献类型：
--
作者：
Tomozawa, S;Nagawa, H;Muto, T
非甾体类抗炎药（NSAIDs）通过抑制环氧化酶（考克斯）而减少结直肠肿瘤的发生。考克斯是花生四烯酸转化为洋地黄素的关键酶，考克斯有两种异构体，考克斯-1和考克斯-2。多项研究表明，考克斯-2在结直肠肿瘤中高水平表达，并在结直肠肿瘤发生中发挥作用。最近有报道选择性抑制考克斯-2抑制结肠癌细胞生长。在这项研究中，我们研究了选择性考克斯-2抑制剂（JTE-522）对结肠癌血行转移的影响。为此目的，我们选择了组成型表达考克斯-2蛋白的鼠结肠癌细胞系colon-26。亚克隆P表达高水平的考克斯-2，亚克隆5表达低水平。将colon-26亚克隆注射到BALB/c小鼠的尾静脉中。从癌细胞注射前一天开始每天腹膜内给予JTE-522，并在细胞注射后16天处死小鼠。在有和没有JTE-522的组之间比较肺转移。在注射亚克隆P的小鼠中，治疗组的肺转移结节数量显著减少。然而，在注射亚克隆5的小鼠中，对照组和治疗组之间几乎没有差异。这些结果表明，抑制结肠癌的血行转移和选择性抑制考克斯-2之间可能存在直接联系，并且选择性考克斯-2抑制剂可能是一类不仅用于结肠直肠肿瘤发生而且用于结肠癌血行转移的新型治疗剂。(C)1999年癌症研究运动。
It is proposed that non-steroidal anti-inflammatory drugs (NSAIDs) reduce colorectal tumorigenesis by inhibition of cyclooxygenase (COX). COX is a key enzyme in the conversion of arachidonic acid to prostaglandins and two isoforms of COX have been characterized, COX-1 and COX-2, Multiple studies have shown that COX-2 is expressed at high levels in colorectal tumours and play a role in colorectal tumorigenesis. Recently it has been reported that selective inhibition of COX-2 inhibits colon cancer cell growth. In this study we investigated the effect of a selective COX-2 inhibitor (JTE-522) on haematogenous metastasis of colon cancer. For this purpose, we selected a murine colon cancer cell line, colon-26, that constitutively expresses the COX-2 protein. The subclone P expressed a high level of COX-2 and the subclone 5 expressed a low level. The colon-26 subclones were injected into the tail vein of BALB/c mice. JTE-522 was given intraperitoneally every day from the day prior to cancer cell injection, and the mice were sacrificed 16 days after cell injection. Lung metastases were compared between groups with and without JTE-522. In the mice injected with subclone P, the number of lung metastatic nodules was significantly reduced in the treated group. However, in the mice injected with subclone 5, there was little difference between the control and the treated groups. These results indicate that there may be a direct link between inhibition of haematogenous metastasis of colon cancer and selective inhibition of COX-2, and that selective COX-2 inhibitors may be a novel class of therapeutic agents not only for colorectal tumorigenesis but also for haematogenous metastasis of colon cancer. (C) 1999 Cancer Research Campaign.