Feng Xue-quan, Wang Jin-huan, Xu Xin-nü, Zhang Biao, Wang Shu-jie, Liu Hong-sheng, Lin Na
Department of Neurosurgery, Tianjin First Central Hospital, Tianjin 300192, China.
Zhonghua Zhong Liu Za Zhi. 2010 Oct;32(10):725-8.
To study the anti-glioma effect of recombinant adenovirus mediated combined gene therapy of bFGF-siRNA and HIV1-Vpr in vivo.
Mouse glioma model was established by injecting 5 × 10(6) LN229 cells into BALB/c-nu nude mice. 30 nude mice were randomly divided into 5 groups: the negative control group, mock group, bFGF-siRNA group, Vpr group and combined therapy group, which at regular intervals were injected with PBS, rAd5-null, rAd5-bFGF-siRNA, rAd5-Vpr, rAd5-bFGF-siRNA plus rAd5-Vpr, respectively. The tumor volume was recorded every third day to draw a growth curve. After four weeks treatment, the mice were killed and specimens were taken. HE, immunohistochemical and TUNEL staining were performed to observe the cell morphology, detect the changes of relevant target proteins and cell apoptosis, respectively. Also the ultrastructural changes were observed by electron microscopy.
The tumor growth inhibition rates were 36.9%, 37.2% and 58.6% in the bFGF-siRNA group, Vpr group and combined therapy group, respectively, and the combined therapy group showed the most significant effect (P < 0.05). Also the results of HE, immunohistochemical and TUNEL staining revealed that the combined therapy group had the best effects on proliferation inhibition and apoptosis induced in glioma cells (P < 0.05). The most significant ultrastructural changes were observed in the combined therapy group.
The combined gene therapy of bFGF-siRNA with Vpr shows a prominent and synergistic anti-glioma effect compared with that of mono-gene therapy in nude mice.
研究重组腺病毒介导的bFGF-siRNA与HIV1-Vpr联合基因治疗在体内的抗胶质瘤作用。
将5×10(6)个LN229细胞注射到BALB/c-nu裸鼠体内建立小鼠胶质瘤模型。30只裸鼠随机分为5组：阴性对照组、空载体组、bFGF-siRNA组、Vpr组和联合治疗组，分别定期注射PBS、rAd5-空载体、rAd5-bFGF-siRNA、rAd5-Vpr、rAd5-bFGF-siRNA加rAd5-Vpr。每三天记录一次肿瘤体积以绘制生长曲线。治疗四周后，处死小鼠并取材。分别进行HE、免疫组化和TUNEL染色，以观察细胞形态、检测相关靶蛋白变化和细胞凋亡情况。同时通过电子显微镜观察超微结构变化。
bFGF-siRNA组、Vpr组和联合治疗组的肿瘤生长抑制率分别为36.9%、37.2%和58.6%，联合治疗组效果最显著（P<0.05）。HE、免疫组化和TUNEL染色结果也显示，联合治疗组对胶质瘤细胞增殖抑制和诱导凋亡的效果最佳（P<0.05）。联合治疗组观察到最显著的超微结构变化。
与单基因治疗相比，bFGF-siRNA与Vpr联合基因治疗在裸鼠中显示出显著的协同抗胶质瘤作用。
