Combined Antitumor Effect of Ad-bFGF-siRNA and Ad-Vpr on the Growth of Xenograft Glioma in Nude Mouse Model

• DOI: 10.1007/s12253-010-9303-5
• Publication Date: 2010-09-16T14:28:49Z
• Authors: Biao Zhang; Xuequan Feng; Jinhuan Wang; Xinnu Xu; Na Lin; Hongsheng Liu
• Keywords: 0301 basic medicine; Brain Neoplasms; Gene Products, vpr; Genetic Vectors; Mice, Nude; Antineoplastic Agents; Apoptosis; Genetic Therapy; Glioma; Xenograft Model Antitumor Assays; Adenoviridae; 3. Good health; Mice; 03 medical and health sciences; Animals; Fibroblast Growth Factor 2; RNA, Small Interfering; Cell Proliferation

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.