Background: Adenoviral based gene therapy has been used in clinical trials in control of advanced prostate cancer. In this study, a promising conditionally replicating adenovirus (CRAd) driven by a tissue specific bone sialoprotein promoter in controlling prostate cancer both in vitro and in vivo is demonstrated. Methods: C4-2B, an androgen-independent prostate cancer cell line, was treated with PBS, Ad-BSP-TK, or the Ad-BSP-E1a in vitro, and in subcutaneous and intraosseous xenographs. Cell proliferation, PSA level in condition medium, tumor volume, and/or serum PSA were followed. Results: The growth of C4-2B and the PSA production was dramatically suppressed by Ad-BSP-E1a at very low dosage (0.3 MOI) compared with PBS and Ad-BSP-TK treatment in vitro. In the subcutaneous model, the tumor volume was significantly lower statistically in the Ad-BSP-E1a treated group than the Ad-BSP-TK control group (P = 0.02). In the intraosseous model, the mice treated in the Ad-BSP-E1a treatment group demonstrated a significant lower PSA compared to that in the control group (P < 0.01) at week 8 and week 16 post-treatment. Conclusions: The CRAd Ad-BSP-E1a revealed potential in treating prostate cancer in this model system. Using viral or none-viral mediated gene therapy to treat prostate carcinoma continues to be a potential avenue to treat afflicted men with prostate cancer.
|Original language||English (US)|
|Number of pages||10|
|Journal||Urologic Oncology: Seminars and Original Investigations|
|State||Published - Nov 2011|
Bibliographical noteFunding Information:
This work was supported by the United States Department of Defense award (CDMRP: Congressional Directed Medical Research Program): DAMD 17-01-1-0107 and DAMD 17-02-1-0148 (to K.S.K.), and DOD Consortium Award PCRP 02 (K.S.K. Sub PI). In addition, private funds from University of Texas Southwestern and Minnesota Department of Urology start-up, Minnesota Medical Foundation (MMF) Dougherty Chair in Urology-Oncology, and MMF Prostate Cancer Research funds helped complete these studies, and provided administrative support.
- Gene therapy
- Prostate cancer