Urology Medical News about CXCR4 antagonist; CTCE-9908; Bcl-2; apoptotic; therapeutic

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Effects of CXCR4 antagonist CTCE-9908 on prostate tumor growth
The Prostate, 07/10/09

Porvasnik S et al. - In a study to further elucidate the relationship between Bcl-2 and CXCR4, it was found 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.

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.
In the xenograft model, CTCE-9908 delivered via daily intraperitoneal injections resulted in a statistically significant reduction in tumor size vs control (396 + 205 mm3 vs 1010 + 215 mm3 respectively) 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.

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