Inhibition of Androgen-Independent Growth of Prostate Cancer by siRNA-Mediated Androgen Receptor Gene Silencing
Abstract
In current period, We first used a signal intra-tumoral injection of different amount of AAV particles to define a proper dosage for efficient virus distribution and knockdown of AR expression. The defined dose was 5.0 x 10^6 AAV particles per 100 mm^3 of tumor volume. Next, we used this dose to treat prostate cancer xenografts. We found that intra-tumoral injection of the ARHP8 but not GFP AAVs abolished tumor growth in LNCaP- and C4-2-derived xenografts in both castrated and shamoperated mice. Immunostaining results confirmed that the AR expression was dramatically down-regulated in AAV.ARHP8-injected tumors. In addition, a significant increase of apoptosis index (TUNEL assay) and dramatic decrease of proliferation index (BrdU incorporation assay) were found in AAV.ARHP8-injected tumors compared to the GFP control. These results demonstrated that the AR is critical for androgen-dependent survival and tumor growth in prostate cancer. Next year, we will repeat these experiments using two more prostate cancer cell line-derived xenografts.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2006
- Accession Number
- ADA462862
Entities
People
- Benyi Li
Organizations
- University of Kansas Medical Center