A vasoactive intestinal peptide antagonist inhibits non-small cell lung cancer growth

T. W. Moody, F. Zia, M. Draoui, D. E. Brenneman, M. Fridkin, A. Davidson, I. Gozes

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)4345-4349
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number10
DOIs
StatePublished - 1993
Externally publishedYes

Keywords

  • cAMP
  • vasoactive intestinal peptide receptors

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