Abstract
The effects vasoactive intestinal peptide (VIP) antagonists were investigated on pancreatic cancer cell lines. (N-Stearyl, Norleucine17) VIP hybrid ((SN)VIPhyb) inhibited 125I-VIP binding to human Capan-2 cells with an IC50 value of 0.01 microM whereas VIP hybrid had an IC50 value of 0.2 microM. By RT-PCR and Northern blot, VPAC1 receptor mRNA was detected in CAPAN-2 cells. One microM (SN)VIPhyb and 10 microM VIPhyb inhibited the ability of 30 nM VIP to elevate cyclic AMP and increase c-fos mRNA. (SN)VIPhyb, 1 microM inhibited the clonal growth of CAPAN-2 cells in vitro. In vivo, (SN)VIPhyb (10 microg/day s.c.) inhibited CAPAN-2 xenograft growth in nude mice. These results indicate that (SN)VIPhyb is a pancreatic cancer VPAC receptor antagonist.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Binding, Competitive
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Cell Division / drug effects
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Cyclic AMP / metabolism
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Genes, fos / genetics
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Humans
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Inhibitory Concentration 50
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Mice
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Mice, Nude
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Molecular Sequence Data
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Neoplasm Transplantation
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Pancreatic Neoplasms / drug therapy
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Pancreatic Neoplasms / metabolism
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Pancreatic Neoplasms / pathology*
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Protein Binding
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Vasoactive Intestinal Peptide / antagonists & inhibitors*
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Receptors, Vasoactive Intestinal Peptide / genetics
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Receptors, Vasoactive Intestinal Peptide / metabolism
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Receptors, Vasoactive Intestinal Polypeptide, Type I
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Transplantation, Heterologous
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Tumor Cells, Cultured
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Vasoactive Intestinal Peptide / antagonists & inhibitors
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Vasoactive Intestinal Peptide / metabolism
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Vasoactive Intestinal Peptide / pharmacology*
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Vasoactive Intestinal Peptide / therapeutic use
Substances
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RNA, Messenger
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Receptors, Vasoactive Intestinal Peptide
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Receptors, Vasoactive Intestinal Polypeptide, Type I
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stearyl-norleucine(17)-vasoactive intestinal peptide
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Vasoactive Intestinal Peptide
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Cyclic AMP