A VASOACTIVE-INTESTINAL-PEPTIDE ANTAGONIST INHIBITS NONSMALL CELL LUNG-CANCER GROWTH

The most prevalent lung cancer, non-small cell lung cancer (NSCLC) has receptors for vasoactive intestinal peptide (VIP). Here the effects of a VIP antagonist (VIPhyb) on NSCLC growth were investigated. In vivo, when VIPhyb (10 mug, s.c.) was daily injected into nude mice, xenograft formation was significantly inhibited by almost-equal-to 80%. In vitro, VIP (100 nM) stimulated colony formation almost-equal-to 2-fold, whereas 1 muM VIPhyb inhibited colony formation by almost-equal-to 50% when adenocarcinoma cell line NCI-H838 was used. The attenuation of tumor proliferation is receptor mediated, as VIPhyb inhibited specific I-125-labeled VIP binding to cell lines NCI-H157 and NCI-H838 with an IC50 of 0.7 muM. VIP (10 nM) increased the cAMP levels 5-fold when cell line NCI-H838 was used, and 10 muM VIPhyb inhibited the increase in cAMP caused by VIP. Northern blot analysis and radioimmunoassays have shown VIP mRNA and VIP-like immunoreactivity in NSCLC cells. These data suggest that VIP may be a regulatory peptide in NSCLC and that VIPhyb is a VIP receptor antagonist that inhibits proliferation.