Molecular Modulation of Inhibitors of Apoptosis as a Novel Approach for Radiosensitization of Human Prostate Cancer
Annual rept. 15 Oct 2007-14 Oct 2008
MICHIGAN UNIV ANN ARBOR
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The major goal of the project is to investigate the radiosensitization activity and mechanism of action of novel IAP-inhibitors in prostate cancer. In the third year of the project, we have investigated the in vivo radiosensitization activity of our lead IAPinhibitors, SH-130 and Embelin, and mechanism of action in human prostate cancer xenograft model. IAP-inhibitors potently enhanced radiation-induced tumor growth inhibition, together with increased induction of apoptosis. In nude mouse xenograft models, IAP-inhibitors Embelin and SH-130 potently sensitized the DU-145 tumors to X-ray radiation. Mechanism studies show that NK-kB pathway activation was also inhibited in the combination therapy. Interestingly, we also observed anti-angiogenic effect of the combination treatment. Due to the lab move in March, 2008, together with our animal room moved and more importantly the move of our X-ray irradiator at the same time, our animal experiments were delayed. We have requested and obtained approval a one year no-cost extension for finish the planned animal and MOA studies.
- Anatomy and Physiology
- Medicine and Medical Research