Enhancing the Anti-Tumor Activity of ErbB Blockers with Histone Deaccetylase (HDAC) Inhibition in Prostate Cancer Cell Lines
Abstract
Characterize the capacity of HDAC inhibitors to enhance the anti-tumor activity of anti-ErbBeta agents in prostate cancer cell lines. Interactions between these agents will be examined at both the cell signaling level, as well as through biologic end-points, including cellular proliferation, impact on cell cycle kinetics, invasion, and angiogenesis. HDAC inhibitors attenuate ErbBeta expression and the combination of HDAC inhibition and ErbBeta blockade resulted in near complete abrogation of EGFR and AKT signaling in the prostate cancer cell lines. HDAC inhibitors enhanced anti-proliferative effects and apoptosis induction of ErbBeta blockade in multiple cell lines. Preliminary gene expression profiles using cDNA arrays suggests multiple levels of potential synergy between ErbBeta and HDAC inhibitors. Continuing work with additional prostate cancer cell lines and examining other biologic end-points, including cell cycle kinetics, angiogenesis, and invasion. Promising results will then be evaluated in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2005
- Accession Number
- ADA458444
Entities
People
- Paul M. Harari
- Prakash Chinnaiyan
Organizations
- University of Wisconsin–Madison