Antagonists of bombesin/gastrin-releasing peptide decrease the expression of angiogenic and anti-apoptotic factors in human glioblastoma

Anticancer Drugs. 2005 Feb;16(2):159-65. doi: 10.1097/00001813-200502000-00007.


We have investigated the antitumor effects and the mechanism of action of antagonists of bombesin/gastrin-releasing peptide (GRP), RC-3940-II and RC-3940-Et, on the growth of U-118MG human malignant glioma xenografted into nude mice. Tumors volume was measured weekly, and after 6 weeks of treatment with GRP antagonists the tumors were analyzed by Western blot assays for the expression of vascular endothelial growth factor (VEGF), protein kinase C (PKC)-alpha, the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax. A radioreceptor assay was used to characterize the receptors for bombesin/GRP. Specific high-affinity receptors for bombesin were found in U-118MG tumors, and their growth was reduced by 52.5% by RC-3940-II and 72.6% by RC-3940-Et (both p<0.01). The tumor doubling time was prolonged by 4.6 and 12 days after treatment with RC-3940-II and RC-3940-Et, respectively, compared to controls (p<0.05). Both antagonists caused a significant (p<0.05) decrease of about 28% in the levels of VEGF protein and a reduction of approximately 35% in the expression of PKCalpha. The relative ratio of Bcl-2:Bax was also diminished by around 70% by both analogs, indicating a net apoptotic gain and the efficacy of treatment. Our results suggest that bombesin/GRP antagonists, RC-3940-II and RC-3940-Et, could be of value for the treatment of human glioblastomas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Bombesin / analogs & derivatives*
  • Bombesin / antagonists & inhibitors*
  • Bombesin / pharmacology
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Gastrin-Releasing Peptide / antagonists & inhibitors*
  • Glioblastoma / blood supply
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Peptide Fragments / pharmacology*
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C-alpha
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Radioligand Assay
  • Receptors, Bombesin / metabolism
  • Transplantation, Heterologous
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / biosynthesis
  • bcl-2-Associated X Protein


  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • BAX protein, human
  • Bax protein, mouse
  • Peptide Fragments
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Bombesin
  • Vascular Endothelial Growth Factor A
  • bcl-2-Associated X Protein
  • bombesin(6-14), Hca(6)-Leu(13)-psi(CH2N)-Tac(14)-
  • Gastrin-Releasing Peptide
  • PRKCA protein, human
  • Prkca protein, mouse
  • Protein Kinase C
  • Protein Kinase C-alpha
  • Bombesin