A vasoactive intestinal peptide antagonist inhibits non-small cell lung cancer growth.
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.
Moody
T W
TW
Department of Biochemistry and Molecular Biology, George Washington University School of Medicine, Washington, DC 20037.
Zia
F
F
Draoui
M
M
Brenneman
D E
DE
Fridkin
M
M
Davidson
A
A
Gozes
I
I
D000595:Amino Acid Sequence; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression; D006131:Growth Inhibitors; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009496:Neurotensin; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011964:Receptors, Gastrointestinal Hormone / Q000037:antagonists & inhibitors*; D018005:Receptors, Vasoactive Intestinal Peptide; D011993:Recombinant Fusion Proteins; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism
D006131:Growth Inhibitors; D010455:Peptides; D012333:RNA, Messenger; D011964:Receptors, Gastrointestinal Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D011993:Recombinant Fusion Proteins; C069189:(VIP-neurotensin) hybrid antagonist; D014660:Vasoactive Intestinal Peptide; D009496:Neurotensin