TY - JOUR
T1 - A vasoactive intestinal peptide antagonist inhibits non-small cell lung cancer growth
AU - Moody, Terry W.
AU - Zia, Farah
AU - Draoui, Muriel
AU - Brenneman, Douglas E.
AU - Fridkin, Mati
AU - Davidson, Ariane
AU - Gozes, Illana
PY - 1993/5/15
Y1 - 1993/5/15
N2 - 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 VTPhyb (10 μg, s.c.) was daily injected into nude mice, xenograft formation was significantly inhibited by ≈80%. In vitro, VIP (100 nM) stimulated colony formation ≈2-fold, whereas 1 μM VIPhyb inhibited colony formation by ≈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 μM. VIP (10 nM) increased the cAMP levels 5-fold when cell line NCI-H838 was used, and 10 μM 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.
AB - 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 VTPhyb (10 μg, s.c.) was daily injected into nude mice, xenograft formation was significantly inhibited by ≈80%. In vitro, VIP (100 nM) stimulated colony formation ≈2-fold, whereas 1 μM VIPhyb inhibited colony formation by ≈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 μM. VIP (10 nM) increased the cAMP levels 5-fold when cell line NCI-H838 was used, and 10 μM 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.
KW - Vasoactive intestinal peptide receptors
KW - cAMP
UR - http://www.scopus.com/inward/record.url?scp=0027276302&partnerID=8YFLogxK
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AN - SCOPUS:0027276302
SN - 0027-8424
VL - 90
SP - 4345
EP - 4349
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 10
ER -
