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    Proc Natl Acad Sci U S A. 1993 May 15;90(10):4345-9.

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

    Moody TW, Zia F, Draoui M, Brenneman DE, Fridkin M, Davidson A, Gozes I.

    Department of Biochemistry and Molecular Biology, George Washington University School of Medicine, Washington, DC 20037.

    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 micrograms, s.c.) was daily injected into nude mice, xenograft formation was significantly inhibited by approximately 80%. In vitro, VIP (100 nM) stimulated colony formation approximately 2-fold, whereas 1 microM VIPhyb inhibited colony formation by approximately 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 microM. VIP (10 nM) increased the cAMP levels 5-fold when cell line NCI-H838 was used, and 10 microM 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.

    PMID: 8389448 [PubMed - indexed for MEDLINE]

    PMCID: 46507

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