lys-pro-arg-arg-pro-tyr-vip(7-28) and Breast-Neoplasms

The effects of vasoactive intestinal peptide (VIP) antagonists on breast cancer cells were investigated. (N-stearyl, norleucine17)VIP hybrid ((SN)VIPhyb) inhibited specific 125I-VIP binding to MCF7, SKBR3, T47D ZR75-1 and MDA-MB231 cells with high affinity (IC50 values of 0.03-0.06 microM). (SN)VIPhyb, 1 microM, inhibited the ability of 10 nM VIP to cause elevation of cAMP and to increase c-fos mRNA. Micromolar concentrations of (SN)VIPhyb inhibited 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 doxorubicin to inhibit breast cancer growth. Using nude mice bearing MDA-MB231 xenografts, VIPhyb potentiated the ability of taxol to inhibit proliferation. The results indicate that VIP receptor antagonists increase the ability of chemotherapeutic drugs to kill breast cancer cells.

Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Breast Neoplasms; Cell Division; Cyclic AMP; Disease Models, Animal; Doxorubicin; Drug Synergism; Female; Genes, fos; Humans; Iodine Radioisotopes; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular Sequence Data; Neurotensin; Paclitaxel; Protein Binding; Receptors, Vasoactive Intestinal Peptide; Recombinant Fusion Proteins; RNA, Messenger; Thymidine; Transplantation, Heterologous; Tumor Cells, Cultured; Vasoactive Intestinal Peptide