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

@article{citeulike:5344904, abstract = {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.}, author = {Anai, Satoshi and Sakamoto, Noboru and Sakai, Yoshihisa and Tanaka, Motoyoshi and Porvasnik, Stacy and Urbanek, Cydney and Cao, Wengang and Goodison, Steve and Rosser, Charles J.}, citeulike-article-id = {5344904}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.urolonc.2009.04.009}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S1078143909001355}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19576799}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19576799}, day = {2}, doi = {10.1016/j.urolonc.2009.04.009}, issn = {10781439}, journal = {Urologic oncology}, keywords = {angiogenesis, dual-targeting, tumor}, month = {July}, posted-at = {2009-11-15 04:53:24}, priority = {2}, title = {Dual targeting of Bcl-2 and VEGF: A potential strategy to improve therapy for prostate cancer.}, url = {http://dx.doi.org/10.1016/j.urolonc.2009.04.009}, year = {2009} }

TY - JOUR ID - citeulike:5344904 L3 - citeulike-article-id:5344904 N2 - 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. JF - Urologic oncology SN - 10781439 TI - Dual targeting of Bcl-2 and VEGF: A potential strategy to improve therapy for prostate cancer. KW - angiogenesis KW - dual-targeting KW - tumor AU - Anai, Satoshi AU - Sakamoto, Noboru AU - Sakai, Yoshihisa AU - Tanaka, Motoyoshi AU - Porvasnik, Stacy AU - Urbanek, Cydney AU - Cao, Wengang AU - Goodison, Steve AU - Rosser, Charles PY - 2009/07/02/ UR - http://dx.doi.org/10.1016/j.urolonc.2009.04.009 ER -