RGD Reference Report - Dual targeting of Bcl-2 and VEGF: A potential strategy to improve therapy for prostate cancer. - Rat Genome Database

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Dual targeting of Bcl-2 and VEGF: A potential strategy to improve therapy for prostate cancer.

Authors: Anai, S  Sakamoto, N  Sakai, Y  Tanaka, M  Porvasnik, S  Urbanek, C  Cao, W  Goodison, S  Rosser, CJ 
Citation: Anai S, etal., Urol Oncol. 2009 Jul 2.
RGD ID: 2315459
Pubmed: PMID:19576799   (View Abstract at PubMed)
DOI: DOI:10.1016/j.urolonc.2009.04.009   (Journal Full-text)

We previously demonstrated that Bcl-2 overexpression stimulates angiogenesis in PC-3 human prostate cancer cells, thus giving these tumors a growth advantage. To further elucidate the relationship between Bcl-2 and vascular endothelial growth factor (VEGF) in PC-3-Bcl-2 cells, tumorigenicity and angiogenesis were evaluated in our in vitro and in vivo model 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 the combination of ASO and bevacizumab. Protein-based assays (e.g., immunohistochemical staining and enzyme-linked immunosorbent assay [ELISA]) were utilized to detect molecular changes. Interestingly, targeting Bcl-2 with ASO resulted in the inhibition of in vitro tube formation and inhibition of angiogenesis in Matrigel plugs similar to treatment with bevacizumab. In our 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. These findings confirm that Bcl-2 is a pivotal target for cancer therapy and thus, further study of this novel combination of Bcl-2 reduction and angiogenic targeting in human tumors is warranted.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate cancer  IMP 2315459 RGD 
prostate cancer  ISOVEGFA (Homo sapiens)2315459; 2315459 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Vegfa  (vascular endothelial growth factor A)

Genes (Mus musculus)
Vegfa  (vascular endothelial growth factor A)

Genes (Homo sapiens)
VEGFA  (vascular endothelial growth factor A)


Additional Information