Conditionally replicating adenovirus therapy utilizing bone sialoprotein promoter (Ad-BSP-E1a) in an in vivo study of treating androgen-independent intraosseous prostate cancer.

Abstract

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.

• Authors: Yingming Li, Michael Kacka, Melissa Thompson, Jer-Tsong Hsieh, Kenneth S Koeneman
• Journal: Urologic oncology (Urol Oncol) 2011 Nov-Dec Vol. 29 Issue 6 Pg. 624-33 ISSN: 1873-2496 [Electronic] United States
• PMID: 19963408 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Adenovirus E1A Proteins
• Osteopontin

Topics

• Adenocarcinoma (drug therapy, secondary)
• Adenoviridae (genetics)
• Adenovirus E1A Proteins (genetics, therapeutic use)
• Animals
• Bone Neoplasms (drug therapy, secondary)
• Cell Line, Tumor
• Genetic Therapy (methods)
• Genetic Vectors
• Humans
• Male
• Mice
• Mice, Nude
• Osteopontin (genetics)
• Promoter Regions, Genetic (genetics)
• Prostatic Neoplasms (pathology, therapy)
• Xenograft Model Antitumor Assays