Prostaglandin E-2 and vasoactive intestinal peptide increase vascular endothelial cell growth factor mRNAs in lung cancer cells

The effects of prostaglandin E-2 (PGE(2)) and vasoactive intestinal peptide (VIP) on vascular endothelial cell growth factor (VEGF) mRNAs were investi gated using lung cancer cells. By RT-PCR, VEGF(121), VEGF(165), and VEGF(18 9), but not VEGF(206) isoforms were detected in all lung cancer cell lines and biopsy specimens examined. By Northern blot. VEGF mRNA was detected in all small cell lung cancer (SCLC) and non-SCLC (NSCLC) cell lines examined. PGE,. VIP and forskolin caused increased VEGF expression in a time- and co ncentration-dependent manner using NSCLC cell line NCI-H157. Approximately 1 muM PGE(2). 0.1 muM VIP and 50 muM forskolin caused cAMP elevation. 64-, 33- and 128-fold, respectively, using NCI-H157 cells after 5 min. The incre ase in cAMP caused by PGE(2) and VIP was reversed by somatostatin (SST). Al so 1 muM PGE(2). 0.1 muM VIP and 50 muM forskolin increased the VEGF mRNA 2 .0-. 1.5- and 2.3-fold, respectively. after 4 h. The increase in VEGF mRNA caused by PGE(2), VIP and forskolin was inhibited by H-89. a protein kinase A inhibitor. A VIP receptor antagonist. VlPhybrid. inhibited the increase in cAMP and VEGF mRNA caused by VIP. By ELISA, VEGF was detected in the con ditioned media exposed to the lung cancer cell lines. These results suggest that VEGF synthesis ill and secretion from lune cancer cells can be regula ted by agents, which cause adenylyl cyclase activation. (C) 2001 Elsevier S cience Ireland Ltd. All rights reserved.