Molecular Modulation of Inhibitors of Apoptosis as a Novel Approach for Radiosensitization of Human Prostate Cancer
Abstract
The major goal of the project is to investigate the radiosensitizationactivity and mechanism of action of novel IAP-inhibitors in prostate cancer. In the second year of the project, we have investigated the in vivo radiosensitization activity of our lead IAPinhibitors, SH-130 and Embelin, in human prostate cancer cell xenograft model. IAP-inhibitorspotently enhanced radiationinduced tumor growth inhibition. In nude mouse xenograft models, IAP-inhibitors Embelin and SH-130 potently sensitized the DU-145 tumors to X-ray radiation. Bioluminescence imaging confirmed SH-130 plus radiation resulted in complete tumor regression in 6 out of 10 tumors, comparing 2/10 tumors with radiation alone, and 0/10 tumors with SH-130 alone. Mechanism studies show that NK-kB pathway activation was also inhibited in the combination therapy. Based on our exciting data obtained from this PCRP project, together with data from other collaborators, we are working with FDA for IND filing aiming for Phase I clinical trial with SH-130 as radiosensitizer for prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2007
- Accession Number
- ADA477422
Entities
People
- Liang Xu
Organizations
- University of Michigan