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

Satoshi Anai, Noboru Sakamoto, Yoshihisa Sakai, Motoyoshi Tanaka, Stacy Porvasnik, Cydney Urbanek, Wengang Cao, Steve Goodison, Charles J. Rosser

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)421-429
Number of pages9
JournalUrologic Oncology: Seminars and Original Investigations
Volume29
Issue number4
DOIs
StatePublished - Jul 1 2011

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Keywords

  • Angiogenesis
  • Bcl-2
  • Therapeutic
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Urology

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