AH6809 antagonizes non-small cell lung cancer prostaglandin receptors.

The effects of prostaglandin (PG)E2 on lung cancer cells were investigated. 3H-PGE2 bound with high affinity to membranes derived from small cell lung cancer (SCLC) and non-SCLC (NSCLC) cell lines. Using NSCLC NCI-H1299 membranes, specific 3H-PGE2 binding to NCI-H1299 membranes was inhibited with moderate affinity by PGE2, PGE1, PGF2alpha and 6-isopropoxy-9-xanthone-2-carboxylic acid (AH6809) but not PGD2, LTB4 or 5-HETE. By RT-PCR, EP2 receptor PCR products were detected in extracts derived from lung cancer cells. PGE2 caused cAMP elevation in a concentration-dependent manner using NCI-H1299 cells and the increase in cAMP caused by PGE2 was antagonized by AH6809. PGE2 had no effect on cytosolic Ca2+ but PGE2 caused increased c-fos mRNA in NCI-H1299 cells. AH6809 inhibited the proliferation of NCI-H1299 cells using MTT and clonogenic assays. These results indicate that functional PG receptors are present on NSCLC cells which are antagonized by AH6809.