Accelerated Tumor Cell Death by Angiogenic Modifiers
Abstract
Because of the potential synergistic interaction between an anti-angiogenic aminosterol, squalamine, and other angiogenic modifiers such as vascular endothelial growth factor (vEGF) and cytokines that may be released during intermittent androgen withdrawal therapy, we tested extensiviely the interaction between soualamine and VECF for an enhanced cytotoxicity to human prostate cancer cells in vitro and xenografts tumor models in vivo. While in vitro synergistic interaction was demonstrated specifically in human prostate cancer cell lines containing a functional androgen receptor, we encountered difficulty in demonstrating such synergism in vivo for the reason that severe toxicity was noted when VEGF was delivered as an Ad-CMv-TK vector. For this reason, we explored the other possible synergistic interaction between squalamine and castration. Results and Discussion: Squalamine is highly synergistic to castration-induced endothelial destruction when applied at the time of castration. We noted VEGF receptor, flt-l and integrin profile (e.g. a6%4) can predict soualamine response. Prostate cancer cells lacking the expression of these markers may be less responsive to the synergistic ineraction between squalamine and castration. We are currently assessing the possible interaction between squalamine and VEGF and soualamine and androgen status of the cell culture and in animals subjected to castration to evaluate if synergism may exist particularly against the growth of endothelial cells. 14. SUBJECT TERMS 15. NUMBER OF PA GES VECF, squalamine, androgen 29
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA418654
Entities
People
- Leland W. Chung
Organizations
- Emory University