Tumor invasiveness and liver metastasis of colon cancer cells correlated with cyclooxygenase‐2 (COX‐2) expression and inhibited by a COX‐2–selective inhibitor …

WS Chen, SJ Wei, JM Liu, M Hsiao… - … journal of cancer, 2001 - Wiley Online Library
WS Chen, SJ Wei, JM Liu, M Hsiao, J Kou‐Lin, WK Yang
International journal of cancer, 2001Wiley Online Library
Non‐steroidal anti‐inflammatory drugs (NSAIDs) have been reported to reduce the risk and
mortality of colorectal cancer (CRC). Although the exact mechanisms remain unclear, the
inhibition of cyclooxygenase (COX) by NSAIDs appears to abort, if not prevent, CRC
carcinogenesis or metastatic tumor progression. The aim of our study was to investigate the
association between COX‐2 expression and CRC tumor cell invasiveness. The differences
in immunoblot‐detectable COX‐2 protein contents in primary CRCs, metastatic hepatic …
Abstract
Non‐steroidal anti‐inflammatory drugs (NSAIDs) have been reported to reduce the risk and mortality of colorectal cancer (CRC). Although the exact mechanisms remain unclear, the inhibition of cyclooxygenase (COX) by NSAIDs appears to abort, if not prevent, CRC carcinogenesis or metastatic tumor progression. The aim of our study was to investigate the association between COX‐2 expression and CRC tumor cell invasiveness. The differences in immunoblot‐detectable COX‐2 protein contents in primary CRCs, metastatic hepatic lesions and corresponding normal mucosa from the same individual were evaluated in 17 patients. Three different colon cancer cell lines, SW620, Lovo, HT‐29 and a metastatic variant of HT‐29, HT‐29/Inv3, were employed to evaluate COX‐2 expression and prostaglandin E2 (PGE2) production in relation to their invasive abilities in vitro. The effects of a COX‐2–selective inhibitor, etodolac, on cell proliferation and invasive activity were also determined. The results showed that 15 of 17 (88%) metastatic CRC cells from the liver and 14 of 17 (82%) primary CRC tissue exhibited much higher levels of COX‐2 than corresponding adjacent normal mucosa from the same patient. Among those patients with relatively high COX‐2 expression in the primary tumors, almost all exhibited even higher levels of COX‐2 in their hepatic metastases. Among the 4 colon cancer cell lines, HT‐29/Inv3 manifested the highest COX‐2 expression, PGE2 production and in vitro invasive activity. The selective COX‐2 inhibitor, etodolac, could especially exert cytotoxicity and markedly suppress the invasive property and PGE2 production, although not 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. © 2001 Wiley‐Liss, Inc.
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