NONSMALL CELL LUNG-CANCER CYCLOXYGENASE ACTIVITY AND PROLIFERATION ARE INHIBITED BY NONSTEROIDAL ANTIINFLAMMATORY DRUGS

The effects of non-steroidal antiinflammatory drugs (NSAIDs) on non-sm all cell lung cancer (NSCLC) were investigated. Arachidonic acid (AA) was metabolized to prostaglandin E2 (PGE2) in NSCLC cells. NSAIDs such as aspirin or indomethacin reduced PGE2 levels in NCI-H157 and H1263 cells, and the dea ease caused by PGE2 was reversed by epidermal growt h factor (EGF). By RT-PCR, both cyclooxygenase (COX)-1 and COX-2 mRNAs are detected in NCI-H157 and H1264 cells. By Northern analysis, COX-2 mRNA was induced by EGF and phorbol ester: By immunocytochemistry COX -1 and COX-2 enzymes were localized to NSCLC tumors. Aspirin, indometh acin and ibuprofen decreased NSCLC growth in vitro. Aspirin and indome thacin inhibited proliferation of NSCLC xenografts in nude mice. These data suggest that COX enzymes may be important regulatory components of NSCLC.