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Ad-bFGF-siRNA 和 Ad-Vpr 联合对裸鼠移植性脑胶质瘤生长的抗肿瘤作用。

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

机构信息

Clinical Lab, Tianjin Huan Hu Hospital, Tianjin 300060, China.

出版信息

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.

摘要

碱性成纤维细胞生长因子(bFGF)已被证明与神经胶质瘤的分级和临床预后相关,并已确立其作为神经胶质瘤治疗靶点的可能用途。Vpr 已被描述为一种抗肿瘤剂,具有很强的抗肿瘤特性。在这里,我们试图研究 bFGF-siRNA 和 Vpr 基因联合治疗是否会在体外和体内增强对神经胶质瘤的疗效。在仅用 Ad-bFGF-siRNA、仅用 Ad-Vpr 以及两者联合治疗后,我们通过 MTT、PI 和 FITC-AnnexinV 双染色法分别评估了细胞增殖、细胞周期和细胞凋亡的变化。此外,我们还使用裸鼠异种移植神经胶质瘤模型评估了 bFGF-siRNA 和 Vpr 基因治疗联合对神经胶质瘤的体内疗效。与单独用 Ad-bFGF-siRNA 或 Ad-Vpr 治疗相比,联合用 Ad-bFGF-siRNA 和 Ad-Vpr 治疗更能成功抑制细胞增殖。单独用 Ad-Vpr 治疗或联合用 Ad-bFGF-siRNA 和 Ad-Vpr 治疗诱导 G2/M 细胞周期阻滞和细胞凋亡;然而,联合治疗比单独用 Ad-Vpr 治疗更有效。虽然每种单一治疗都可以减缓异种移植神经胶质瘤的生长,但 Ad-bFGF-siRNA 和 Ad-Vpr 的联合治疗优于单独用 Ad-bFGF-siRNA 或 Ad-Vpr 治疗。我们的结果表明,bFGF-siRNA 和 Vpr 基因的联合治疗可以实现增强的抗神经胶质瘤活性,支持这两种抗肿瘤剂联合使用可能为神经胶质瘤治疗开辟新的前景的观点。

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