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Background It has been suggested that pro-inflammatory cytokines play important roles in cancer development and progression. Cytokines have been reported to increase cyclooxygenase-2 (COX-2) expression level and prostaglandins (PGs) production in vascular smooth muscle cells. Administration of non-steroidal anti-inflammatory drugs showed cancer prevention as well as therapeutic activities in several human cancers. However, correlation between COX-2 level and pro-inflammatory cytokines has not been precisely investigated. In this study, we examined whether pro-inflammatory cytokines induce COX-2 expression and PGE2 production in human lung cancer cells. Further, we examined effects of a COX inhibitor, aspirin (ASA), and a COX-2 selective inhibitor, CAY10404 on lung cancer cells. Methods COX-2 expression, PGE2 production and proliferation in 4 non-small cell lung cancer (NSCLC) cell lines including 3 adenocarcinoma cell lines (ABC-1, PC-3 and H2030) and one squamous cell carcinoma cell line (LC-1sq) were examined. Effects of cytokines in combination of interleukin-1β (lL-1β) and tumor necrosis factor-α (TNF-α), and effects of ASA treatment were analyzed by western blots, PGE2 enzyme immuno-assay and MTS assay. To clarify whether cell growth inhibition by ASA was due to apoptosis or necrosis, we performed flow cytometric analysis using an apoptosis detection kit. Results Without addition of cytokines, COX-2 was weakly expressed in ABC-1, PC-3 and H2030. In LC-1sq, COX-2 was not detectable. PGE2 was produced in ABC-1, PC-3 and H2030, however, PGE2 was not detectable in LC-1sq. When cells were treated with IL-1β and TNF-α at a concentration of 5ng /ml, COX-2 and PGE2 was increased in ABC-1, PC-3 and H2030. In contrast, addition of cytokines did not increase the COX-2, however, it slightly stimulated PGE2 in LC-1sq. Addition of these cytokines inhibited cell growth in ABC-1 and LC-1sq inducing necrosis, although these cytokines proliferated PC-3. In H2030, addition of cytokines did not alter the cell proliferation. Addition of ASA induced cell death both in the presence and absence of cytokines in all 4 cell lines. In contrast, CAY10404 did not affect cell proliferation in all cell lines. COX-2 expression showed various change when ASA was added, however, CAY10404 did not affect the protein level in all 4 cell lines. Cytokine-induced PGE2 production was suppressed by ASA and CAY10404 treatment in all cell lines. Conclusions We found that pro-inflammatory cytokines induced COX-2 protein expression and PGE2 production in human lung adenocarcinoma cell lines. Our results suggest that lung adenocarcinoma expresses various levels of functional COX-2 depending on the difference of the environment including existence of pro-inflammatory cytokines. ASA induced cell death in NSCLC cells, however, COX-2 selective inhibitor did not affect the cell proliferation.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]