Abstract
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 mm3 vs. 1,010 + 215 mm3 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.
Original language | English (US) |
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Pages (from-to) | 1460-1469 |
Number of pages | 10 |
Journal | Prostate |
Volume | 69 |
Issue number | 13 |
DOIs | |
State | Published - Sep 15 2009 |
Keywords
- Apoptotic
- Bcl-2
- CTCE-9908
- CXCR4
- Therapeutic
ASJC Scopus subject areas
- Oncology
- Urology