In lung cancer arachidonic acid (AA) is metabolized by cyclooxygenase (COX) enzymes leading to prostaglandin (PG) production. In non-small cell lung cancer (NSCLC) PGE2 is a major product. NSCLC PGE2 levels and proliferation are inhibited by non-steroidal antiinflammatory drugs (NSAIDs) such as aspirin. Proliferation and PGE2 levels are increased by epidermal growth factor (EGF). In particular, EGF increases COX-2 mRNA in NSCLC cell lines NCI-H157, H1264 and H1299. In the present period, PG receptors were characterized in NSCLC cells. 3H-PGE2 bound with high affinity to membranes derived from NSCLC cell line NCI-H1299. Specific 3H-PGE2 binding VEGF mRNA was inhibited by PGE2, PGE1, PGF2a but not PGG2. The order of binding affinity to NCI-H1299 membranes was PGE2 > PGE1 > PGF2a. Specific 3H-PGE2 binding was inhibited by AH6809, a PG antagonist and GTP, which interacts with a stimulatory guanine nucleotide binding subunit. As a result of this interaction adenylyl cyclase was stimulated and the increase in cAMP caused by PGE2 was inhibited by AH6809. Also, AH6809 inhibited the growth of NSCLC cell lines. It remains to be determined if AH6809 will be a therapeutic agent for NSCLC.
