Inhibition of haematogenous metastasis of colon cancer in mice by a selective COX-2 inhibitor, JTE-522

Citation
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
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
BRITISH JOURNAL OF CANCER
ISSN journal
0007-0920 → ACNP
Volume
81
Issue
8
Year of publication
1999
Pages
1274 - 1279
Database
ISI
SICI code
0007-0920(199912)81:8<1274:IOHMOC>2.0.ZU;2-9
Abstract
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.