Abstract
The effects vasoactive intestinal peptide (VIP) antagonists were investigated on pancreatic cancer cell lines. (N-Stearyl, Norleucine 17) VIP hybrid ((SN)VIPhyb) inhibited 125I-VIP binding to human Capan-2 cells with an IC 50 value of 0.01 μM whereas VIPhybrid had an IC 50 value of 0.2 μM. By RT-PCR and Northern blot, VPAC 1 receptor mRNA was detected in CAPAN-2 cells. One μM (SN)VIPhyb and 10 μM VIPhyb inhibited the ability of 30 μM VIP to elevate cyclic AMP and increase c-fos mRNA. (SN)VIPhyb, 1 μM inhibited the clonal growth of CAPAN-2 cells in vitro. In vivo, (SN)VIPhyb (10 μg/day s.c.) inhibited CAPAN-2 xenograft growth in nude mice. These results indicate that (SN)VIPhyb is a pancreatic cancer VPAC receptor antagonist.
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