VIP Receptor Antagonists and Chemotherapeutic Drugs Inhibit the Growth of Breast Cancer Cells

Breast Cancer Res Treat. 2001 Jul;68(1):55-64. doi: 10.1023/a:1017994722130.

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 0.03-0.06 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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Cell Division / drug effects
  • Cyclic AMP / metabolism
  • Disease Models, Animal
  • Doxorubicin / pharmacology
  • Drug Synergism
  • Female
  • Genes, fos / drug effects
  • Humans
  • Iodine Radioisotopes
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Sequence Data
  • Neurotensin / pharmacology*
  • Neurotensin / therapeutic use
  • Paclitaxel / pharmacology
  • Protein Binding / drug effects
  • RNA, Messenger / drug effects
  • Receptors, Vasoactive Intestinal Peptide / antagonists & inhibitors*
  • Receptors, Vasoactive Intestinal Peptide / metabolism
  • Recombinant Fusion Proteins / pharmacology*
  • Recombinant Fusion Proteins / therapeutic use
  • Thymidine
  • Transplantation, Heterologous
  • Tumor Cells, Cultured / drug effects
  • Vasoactive Intestinal Peptide / antagonists & inhibitors*
  • Vasoactive Intestinal Peptide / chemistry
  • Vasoactive Intestinal Peptide / metabolism
  • Vasoactive Intestinal Peptide / pharmacology*
  • Vasoactive Intestinal Peptide / therapeutic use

Substances

  • Antineoplastic Agents
  • Iodine Radioisotopes
  • RNA, Messenger
  • Receptors, Vasoactive Intestinal Peptide
  • Recombinant Fusion Proteins
  • stearyl-norleucine(17)-vasoactive intestinal peptide
  • (VIP-neurotensin) hybrid antagonist
  • Vasoactive Intestinal Peptide
  • Neurotensin
  • Doxorubicin
  • Cyclic AMP
  • Paclitaxel
  • Thymidine