Cyclooxygenase-2 in cancer cells and macrophages induces colon cancer cell growth by cigarette smoke extract.

Cigarette smoking, cyclooxygenase-2 (COX-2) and macrophages are independently associated with colorectal cancer. In the present study, cigarette smoke ethanol extract was applied to colon cancer cells (SW1116) or indirectly via activated macrophages (THP-1 cells) to attest their effects on cancer cell proliferation and tumor growth both in vitro and in vivo. Ethanol extract induced COX-2 expression in SW1116 and THP-1 cells. Combination of THP-1 pre-incubated medium and ethanol extract further potentiated COX-2 expression and proliferation of SW1116 cells. Tumor growth in nude mice was positively associated with the medium and/or ethanol extract treatments, together with the up-regulation of cell proliferation and angiogenesis, and down-regulation of apoptosis. Application of a COX-2 inhibitor (SC236) reduced tumor growth as well as cell proliferation and angiogenesis. These actions are partially depended on the decrease of COX-2 expression. Taken together, inhibition of COX-2 activity may have significant implication to prevent colon cancer in smokers.