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VIP receptor antagonists and chemotherapeutic drugs inhibit the growth of breast cancer cells
Authors:Terry W. Moody  Julius Leyton  Daniel Chan  Douglas C. Brenneman  Mati Fridkin  Edgar Gelber  Albert Levy  Illana Gozes
Affiliation:(1) Cell and Cancer Biology Department, Medicine Branch, National Cancer Institute, Rockville, MD, USA;(2) University Colorado Cancer Centre, Denver, CO, USA;(3) Unit on Neurochemistry, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, Bethesda, MD, USA;(4) Department of Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel;(5) Department of Clinical Biochemisty, Sackler School of Medicine, Tel Aviv, Israel
Abstract:
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 0.03–0.06mgrM). (SN)VIPhyb,1mgrM, inhibited the ability of 10nM 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.
Keywords:antagonist  breast cancer  doxorubicin  proliferation  taxol  VIP
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