Combined therapeutic effects of adenoviral vector-mediated GLIPR1 gene therapy and radiotherapy in prostate and bladder cancer models

Urol Oncol. 2014 Feb;32(2):92-100. doi: 10.1016/j.urolonc.2012.10.007. Epub 2013 Feb 20.

Abstract

Objectives: The objectives of this study are to explore the potential benefits of combining AdGlipr1 (or AdGLIPR1) gene therapy with radiotherapy using subcutaneous prostate and bladder cancer models.

Materials and methods: Combination adenoviral vector-mediated gene therapy and radiotherapy were applied to 178-2 BMA and TSU-Pr1 cells in vitro and colony formation and apoptosis were analyzed. In addition, combination therapies were administered to mice bearing subcutaneous 178-2 BMA and TSU-Pr1 tumors, and tumor growth suppression and survival extension were compared with the monotherapies (AdGlipr1/AdGLIPR1 and radiotherapy) or control vector Adv/CMV/βgal, as well as single-cycle treatment with 2-cycle treatment.

Results: Combination treatment significantly suppressed colony formation and increased apoptosis in vitro. In vivo, combination therapy produced significant 178-2 BMA and TSU-Pr1 tumor growth suppression and survival extension compared with the monotherapies or the control. Further tumor growth suppression and survival extension were observed after 2 cycles of the combination treatment.

Conclusions: Combining AdGlipr1 (AdGLIPR1) with radiotherapy may achieve additive or synergistic tumor control in selected prostate and bladder tumors, and additional therapeutic effects may result with repeated treatment cycles.

Keywords: Bladder cancer; GLIPR1; Gene therapy; Prostate cancer; Radiation therapy.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / radiation effects
  • Male
  • Membrane Proteins
  • Mice
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / therapy
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Radiotherapy / methods*
  • Treatment Outcome
  • Tumor Burden / genetics
  • Tumor Burden / radiation effects
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy*
  • Xenograft Model Antitumor Assays

Substances

  • GLIPR1 protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins