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

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.

• Authors: T W Moody, F Zia, M Draoui, D E Brenneman, M Fridkin, A Davidson, I Gozes
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 90 Issue 10 Pg. 4345-9 (May 15 1993) ISSN: 0027-8424 [Print] United States
• PMID: 8389448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• 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, 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, metabolism)