Neuromedin B receptor antagonist suppresses tumor angiogenesis and tumor growth in vitro and in vivo

Cancer Lett. 2011 Dec 15;312(1):117-27. doi: 10.1016/j.canlet.2011.08.014. Epub 2011 Aug 22.

Abstract

Neuromedin B (NMB), a member of the mammalian bombesin-like peptide family, and its receptor were aberrantly expressed in vascularized solid tumors. Here, the NMB receptor (NMB-R) antagonist PD168368 specifically inhibited both NMB-induced in vivo and in vitro angiogenesis. In addition, PD168368 showed growth inhibitory effects on MDA-MB-231 breast cancer cells by inducing cell cycle arrest and apoptosis. Furthermore, PD168368 effectively suppressed tumor growth in a xenograft model of breast tumor in vivo. Overall, NMB-R antagonist exhibited a significant antitumor activity by simultaneously inhibiting neovascularization and cancer cell growth, thereby suggesting that NMB-R could be a potential therapeutic target for cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / blood supply*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Growth Processes / drug effects
  • Female
  • Humans
  • Indoles / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / pathology
  • Pyridines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Bombesin / antagonists & inhibitors*
  • Receptors, Bombesin / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Indoles
  • PD 168368
  • Pyridines
  • Receptors, Bombesin