Combined antitumor effect of Ad-bFGF-siRNA and Ad-Vpr on the growth of xenograft glioma in nude mouse model

Pathol Oncol Res. 2011 Jun;17(2):237-42. doi: 10.1007/s12253-010-9303-5. Epub 2010 Sep 17.

Abstract

Basic fibroblast growth factor (bFGF) has been demonstrated to correlate with glioma grade and clinical outcome and has established its possible usefulness as a target for glioma therapy. Vpr has been described as an antitumor agent and displays a potent antitumor nature. Here, we try to investigate whether a combined treatment with bFGF-siRNA and Vpr gene would have a enhanced effectiveness on glioma in vitro and in vivo.After treatments with only Ad-bFGF-siRNA, only Ad-Vpr, and a combination of both, we assessed the changes in cell proliferation, cell cycle, and apoptosis in vitro by the methods of MTT, PI and FITC-AnnexinV double staining, respectively. In addition, we also evaluated the combined effect of bFGF-siRNA and Vpr gene therapy on glioma in vivo using xenograft glioma models in nude mice. Combined Ad-bFGF-siRNA and Ad-Vpr treatment was more better successful in inhibiting cell proliferation in comparison with treatments of either Ad-bFGF-siRNA or Ad-Vpr alone. Treatment of Ad-Vpr alone or a treatment of a combination of Ad-bFGF-siRNA and Ad-Vpr induced the G2/M cell cycle arrest and apoptosis; however, combined treatment was more effective than the Ad-Vpr treatment alone. Although each single treatment can slow the growth of xenograft glioma, the combined treatment with Ad-bFGF-siRNA and Ad-Vpr was better than either the Ad-bFGF-siRNA or Ad-Vpr treatment alone. Our results suggest that the combination therapy with bFGF-siRNA and Vpr gene can achieve a enhanced activity of anti-glioma, supporting the idea that the combination of these two antitumor agents could open new perspectives in glioma therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Brain Neoplasms / drug therapy*
  • Cell Proliferation / drug effects
  • Fibroblast Growth Factor 2 / antagonists & inhibitors*
  • Fibroblast Growth Factor 2 / genetics
  • Gene Products, vpr / therapeutic use*
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Glioma / drug therapy*
  • Mice
  • Mice, Nude
  • RNA, Small Interfering / therapeutic use*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Gene Products, vpr
  • RNA, Small Interfering
  • Fibroblast Growth Factor 2