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

Proc Natl Acad Sci U S A. 1993 May 15;90(10):4345-9. doi: 10.1073/pnas.90.10.4345.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Division / drug effects
  • Gene Expression
  • Growth Inhibitors*
  • Humans
  • In Vitro Techniques
  • Lung Neoplasms / pathology*
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Neoplasm Transplantation
  • Neoplasms, Experimental / drug therapy
  • Neurotensin*
  • Peptides / chemistry
  • Peptides / pharmacology*
  • RNA, Messenger / genetics
  • Receptors, Gastrointestinal Hormone / antagonists & inhibitors*
  • Receptors, Vasoactive Intestinal Peptide
  • Recombinant Fusion Proteins
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Vasoactive Intestinal Peptide / antagonists & inhibitors*
  • Vasoactive Intestinal Peptide / metabolism

Substances

  • Growth Inhibitors
  • Peptides
  • RNA, Messenger
  • Receptors, Gastrointestinal Hormone
  • Receptors, Vasoactive Intestinal Peptide
  • Recombinant Fusion Proteins
  • (VIP-neurotensin) hybrid antagonist
  • Vasoactive Intestinal Peptide
  • Neurotensin