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.