S. Tomozawa et al., Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522, BR J CANC, 81(8), 1999, pp. 1274-1279
It is proposed that non-steroidal anti-inflammatory drugs (NSAIDs) reduce c
olorectal tumorigenesis by inhibition of cyclooxygenase (COX). COX is a key
enzyme in the conversion of arachidonic acid to prostaglandins and two iso
forms of COX have been characterized, COX-1 and COX-2, Multiple studies hav
e shown that COX-2 is expressed at high levels in colorectal tumours and pl
ay a role in colorectal tumorigenesis. Recently it has been reported that s
elective inhibition of COX-2 inhibits colon cancer cell growth. In this stu
dy we investigated the effect of a selective COX-2 inhibitor (JTE-522) on h
aematogenous metastasis of colon cancer. For this purpose, we selected a mu
rine colon cancer cell line, colon-26, that constitutively expresses the CO
X-2 protein. The subclone P expressed a high level of COX-2 and the subclon
e 5 expressed a low level. The colon-26 subclones were injected into the ta
il 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 day
s after cell injection. Lung metastases were compared between groups with a
nd without JTE-522. In the mice injected with subclone P, the number of lun
g metastatic nodules was significantly reduced in the treated group. Howeve
r, in the mice injected with subclone 5, there was little difference betwee
n the control and the treated groups. These results indicate that there may
be a direct link between inhibition of haematogenous metastasis of colon c
ancer and selective inhibition of COX-2, and that selective COX-2 inhibitor
s may be a novel class of therapeutic agents not only for colorectal tumori
genesis but also for haematogenous metastasis of colon cancer. (C) 1999 Can
cer Research Campaign.