Effects of CXCR4 antagonist CTCE-9908 on prostate tumor growth

Prostate. 2009 Sep 15;69(13):1460-9. doi: 10.1002/pros.21008.


Background: Recent reports have linked the survival-promoting effect of CXCR4 to the up regulation of Bcl-2 protein expression.

Materials and methods: To further elucidate the relationship between Bcl-2 and CXCR4, tumorigenicity was evaluated in in vitro and in vivo models following treatment with CTCE-9908, a CXCR4 antagonist peptide.

Results: In vitro, CTCE-9908 inhibited cellular proliferation in PC-3-Bcl-2 and PC-3-Neo cell lines Furthermore in our xenograft model, CTCE-9908 delivered via daily intraperitoneal injections resulted in a statistically significant reduction in tumor size compared to control (396 + 205 mm(3) vs. 1,010 + 215 mm(3) respectively, p < 0.05) in the Bcl-2 expressing tumors. This reduction was associated with knockdown of VEGF, inhibition of angiogenesis and lymphangiogenesis, and induction of apoptosis. CTCE-9908 therapy was also associated with a marked reduction in intra-tumoral host cells expressing VEGFR1 and CD11b myeloid-derived suppressor cells (MDSC).

Conclusion: These data show that CXCR4 antagonists represent a valuable addition to the cancer therapeutic arsenal. Such agents may have beneficial synergistic dual-effects in reducing tumor cell proliferation directly, and indirectly through perturbation of the tumor microenvironment. Further studies of the novel CTCE-9908 compound in prostate and other solid tumor inhibition are warranted. Prostate 69: 1460-1469, 2009. (c) 2009 Wiley-Liss, Inc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • CD11b Antigen / metabolism
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Peptides / pharmacology*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • CD11b Antigen
  • CTCE-9908
  • CXCR4 protein, human
  • Peptides
  • Receptors, CXCR4
  • Vascular Endothelial Growth Factor Receptor-1
  • Proto-Oncogene Proteins c-akt