Cyclooxygenase-2 (COX-2), the
prostaglandin (PG)-synthesizing
enzyme overexpressed in
colorectal cancer (CRC), has pleiotropic,
cancer-promoting effects.
COX-2 inhibitors (CIBs) interfere with many
cancer-associated processes and show promising
antineoplastic activity, however, a common mechanism of CIB action has not yet been established. We therefore investigated by microarray the global response towards the CIB
APHS at a dose significantly inhibiting the growth of three COX-2-positive CRC but not of two COX-2-negative cell lines. None of the genes significantly (p = 0.005) affected by
APHS were common to all three cell lines and 83% of the altered pathways were cell line-specific. Quantitative polymerase chain reaction (QPCR) on selected pathways confirmed cell line-specific expression alterations induced by
APHS. A low stringency data analysis approach using BRB array tools coupled with QPCR, however, identified small expression changes shared by all COX-2-positive cell lines in genes related to the WNT pathway, the key driver of colonic
carcinogenesis. Our data indicates a substantial cell line-specificity of
APHS-induced expression alterations in CRC cells and helps to explain the divergent effects reported for CIBs. Further, the shared inhibition of the WNT pathway by
APHS suggests one potential common mechanism behind the
antineoplastic effects of COX-2 inhibition.