Tumor invasiveness and liver metastasis of colon cancer cells correlated with cyclooxygenase-2 (COX-2) expression and inhibited by a COX-2-selective inhibitor, etodolac

Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to reduce the risk and mortality of colorectal cancer (CRC). Although the exact mech anisms remain unclear, the inhibition of cyclooxygenase (COX) by NSAIDs app ears to abort, if not prevent, CRC carcinogenesis or metastatic tumor progr ession. The aim of our study was to investigate the association between COX -2 expression and CRC tumor cell invasiveness. The differences in immunoblo t-detectable COX-2 protein contents in primary CRCs, metastatic hepatic les ions and corresponding normal mucosa from the same individual were evaluate d in 17 patients. Three different colon cancer cell lines, SW620, Love, HT- 29 and a metastatic variant of HT-29, HT-29/Inv3, were employed to evaluate COX-2 expression and prostaglandin E-2 (PGE(2)) production in relation to their invasive abilities in vitro. The effects of a COX-2-selective inhibit or, etodolac, on cell proliferation and invasive activity were also determi ned. The results showed that 15 of 17 (88%) metastatic CRC cells from the l iver and 14 of 17 (82%) primary CRC tissue exhibited much higher levels of COX-2 than corresponding adjacent normal mucosa from the same patient, Amon g those patients with relatively high COX-2 expression in the primary tumor s, almost all exhibited even higher levels of COX-2 in their hepatic metast ases. Among the 4 colon cancer cell lines. HT-29/Inv3 manifested the highes t COX-2 expression, PGE(2) production and in vitro invasive activity. The s elective COX-2 inhibitor, etodolac, could especially exert cytotoxicity and markedly suppress the invasive property and PGE(2) production, although no t the COX-2 protein level, in HT-29/Inv3 cells. Our results imply that COX- 2 expression may be associated with the invasive and metastatic properties of CRC tumor cells. (C) 2001 Wiley-Liss, Inc.