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Dual targeting of Bcl-2 and VEGF: A potential strategy to improve therapy for prostate cancer
Urologic Oncology: Seminars and Original Investigations, 07/29/09

Anai S et al. - In a study to further elucidate the relationship between Bcl-2 and vascular endothelial growth factor (VEGF) in PC-3-Bcl-2 cells, it was reported that Bcl-2 is a pivotal target for cancer therapy and thus, further study of this combination of Bcl-2 reduction and angiogenic targeting in human tumors is warranted.

Methods

Tumorigenicity and angiogenesis were evaluated in in vitro and in vivo models treated with antisense Bcl-2 oligodeoxynucleotide (ASO) and bevacizumab.
In vitro and in vivo angiogenesis assays, as well as a xenograft tumor model of the human prostate cancer cell line PC-3-Bcl-2, were subjected to ASO alone, bevacizumab alone, or combination of ASO and bevacizumab.
Protein-based assays (eg, immunohistochemical staining and enzyme-linked immunosorbent assay [ELISA]) were utilized to detect molecular changes.

Results

Targeting Bcl-2 with ASO resulted in inhibition of in vitro tube formation and inhibition of angiogenesis in Matrigel plugs similar to treatment with bevacizumab.
In a PC-3-Bcl-2 xenograft model, ASO alone resulted in 41% reduction in tumor size, bevacizumab alone resulted in a 50% reduction in tumor size, whereas the combination of ASO with bevacizumab was associated with >95% reduction in tumor volume.
Reduction in tumor size in all groups was associated with reduction in Bcl-2 and VEGF expression, induction of apoptosis, and inhibition of angiogenesis and its associated chemokine production.

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