""""""""Arachidonic acid (AA) is released from non-small cell lung cancer (NSCLC) phospholipids when epidermal growth factor (EGF) binds to NSCLC tyrosine kinase receptors. The AA may be metabolized by cyclooxygenase (COX) to prostaglandins (PGs) or by lipoxygenase (LO) to leukotrienes (LKs). Nordihydroguaiaretic acid (NDGA) inhibits LO activity resulting in decreased NSCLC proliferation. NDGA prevents lung carcinogenesis in A/J mice. In this period, nonsteroidal antiinflammatory drugs (NSAIDs) inhibited PGE2 production in and proliferation of NSCLC cells. The NSAIDs inhibited COX enzymes in NCI-H1264 cells. Also, PGE2 elevated cAMP and stimulated c-fos as well as vascular endothelial cell growth factor (VEGF) mRNAs. VEGF is an angiogenic factor for NSCLC. The increase in cAMP and VEGF mRNA caused by PGE2 is reversed by somatostatin (SST) which inhibits adenylyl cyclase. These results suggest that PG and SST receptors are present on NSCLC cells and that these receptors regulate cAMP and VEGF.""""""""
