(N-stearyl, norleucine17) VIP hybrid inhibits the growth of pancreatic cancer cell lines.
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.
Zia
H
H
Cell and Cancer Biology Dept., Medicine Branch, National Cancer Institute, Rockville, MD 20850, USA.
Leyton
J
J
Casibang
M
M
Hau
V
V
Brenneman
D
D
Fridkin
M
M
Gozes
I
I
Moody
T W
TW
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D016762:Genes, fos / Q000235:genetics; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D012333:RNA, Messenger; D018005:Receptors, Vasoactive Intestinal Peptide; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; C086770:stearyl-norleucine(17)-vasoactive intestinal peptide; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP