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 (VIP-hyb) on NSCLC growth were investigated. In vivo, when VIPhyb (10 μg, s.c.) was daily injected into nude mice, xenograft formation was significantly inhibited by ≃80%. In vitro, VIP (100 nM) stimulated colony formation ≃2-fold, whereas 1 μM VIPhyb inhibited colony formation by ≃50% when adenocarcinoma cell line NCI-H838 was used. The attenuation of tumor proliferation is receptor mediated, as VIPhyb inhibited specific 125I- labeled VIP binding to cell lines NCI-H157 and NCI-H838 with an IC50 of 0.7 μM. VIP (10 nM) increased the cAMP levels 5-fold when cell line NCI-H838 was used, and 10 μM 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.
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - 1993|
- vasoactive intestinal peptide receptors