Enhancing the Anti-tumor Activity of ErbB Blockers with Histone Deaccetylase(HDAC)Inhibition in Prostate Cancer Cell Lines

摘要

Characterize the capacity of HDAC inhibitors to enhance the anti- tumor activity of anti-ErbB 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 ErbB expression near complete abrogation of EGFR and AKT signaling in the prostate cancer cell lines. HDAC inhibitors enhanced antiproliferative effects and apoptosis induction of ErbB blockade in multiple cell lines. Preliminary gene expression profiles using cDNA arrays suggests multiple levels of potential synergy between ErbB 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.