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

Urol Oncol. 2011 Nov-Dec;29(6):624-33. doi: 10.1016/j.urolonc.2009.08.012. Epub 2009 Dec 6.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

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

Substances

  • Adenovirus E1A Proteins
  • Osteopontin