The effects of vasoactive intestinal peptide (VIP) antagonists on breast ca
ncer cells were investigated. (N-stearyl, norleucine(17))VIP hybrid ((SN)VI
Phyb) inhibited specific (1)25I-VIP binding to MCF7, SKBR3, T47D ZR75-1 and
MDA-MB231 cells with high affinity (IC(5)0 values of 0.03-0.06 muM). (SN)V
IPhyb,1 muM, inhibited the ability of 10 nM VIP to cause elevation of cAMP
and to increase c-fos mRNA. Micromolar concentrations of (SN)VIPhyb inhibit
ed the proliferation of MDA-MB231 or MCF7 cells using a MTT and clonogenic
assay. Using a MTT assay, (SN)VIPhyb enhanced the ability of taxol and doxo
rubicin to inhibit breast cancer growth. Using nude mice bearing MDA-MB231
xenografts, VIPhyb potentiated the ability of taxol to inhibit proliferatio
n. The results indicate that VIP receptor antagonists increase the ability
of chemotherapeutic drugs to kill breast cancer cells.