VIP receptor antagonists and chemotherapeutic drugs inhibit the growth of breast cancer cells.
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.
Moody
T W
TW
Cell and Cancer Biology Department, Medicine Branch, National Cancer Institute, Rockville, MD 20850, USA. moodyt@bprb.nci.nih.gov
Leyton
J
J
Chan
D
D
Brenneman
D C
DC
Fridkin
M
M
Gelber
E
E
Levy
A
A
Gozes
I
I
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D016762:Genes, fos / Q000187:drug effects; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009496:Neurotensin / Q000494:pharmacology* / Q000627:therapeutic use; D017239:Paclitaxel / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D013936:Thymidine; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D018005:Receptors, Vasoactive Intestinal Peptide; D011993:Recombinant Fusion Proteins; C086770:stearyl-norleucine(17)-vasoactive intestinal peptide; C069189:(VIP-neurotensin) hybrid antagonist; D014660:Vasoactive Intestinal Peptide; D009496:Neurotensin; D004317:Doxorubicin; D000242:Cyclic AMP; D017239:Paclitaxel; D013936:Thymidine