RNA干扰AKT2的表达对胶质瘤裸鼠移植瘤替莫唑胺敏感性的影响

发布时间：2018-02-27 14:27

本文关键词： 丝/苏氨酸蛋白激酶胶质瘤替莫唑胺　出处：《中华神经外科疾病研究杂志》2016年05期 　论文类型：期刊论文

【摘要】：目的研究RNA干扰丝/苏氨酸蛋白激酶2(AKT2)对脑胶质瘤移植瘤的替莫唑胺疗效的改变。方法构建胶质瘤裸鼠成瘤模型,瘤内注射和腹腔内给替莫唑胺(TMZ)药物,以替莫唑胺化疗药物和AKT2短发夹结构RNA(AKT2-shRNA)表达载体对成瘤后的裸鼠瘤体进行联合干预治疗,进而观察并测量各组裸鼠肿瘤体积大小。DNA断裂的原位末端标记法(TUNEL)测定并计算分析各组裸鼠成瘤后肿瘤组织细胞的凋亡的变化。结果空白对照组、替莫唑胺化疗组、TMZ+阴性对照组、TMZ+AKT2干扰组裸鼠瘤体体积分别为:(669.34±98.73)mm3、(399.86±55.26)mm3、(383.81±34.01)mm3、(297.72±41.49)mm3;瘤体质量分别为:(1.25±0.26)g、(0.72±0.11)g、(0.69±0.07)g、(0.52±0.07)g。TMZ+AKT2干扰组其肿瘤体积及瘤体质量都明显小于空白对照组、替莫唑胺组和TMZ+阴性对照组,有显著性差异(P0.05)。TUNEL实验结果显示:空白对照组、替莫唑胺化疗组、TMZ+阴性对照组、TMZ+AKT2干扰组裸鼠瘤体凋亡指数分别为:7.15%±1.04%、25.26%±2.71%、26.63%±3.46%、42.81%±5.97%。TMZ+AKT2干扰组其肿瘤凋亡情况明显高于空白对照组、替莫唑胺组和TMZ+阴性对照组,结果有显著性差异(P0.05)。结论 RNA干扰AKT2能够显著提高裸鼠胶质母细胞瘤对TMZ化疗的敏感性。
[Abstract]:Objective to study the effect of RNA interference filament / threonine protein kinase 2AKT2 on the therapeutic effect of temozolidomide on glioma transplanted tumor. Methods the tumor model of nude mice with glioma was established by intratumoral injection and intraperitoneal administration of temozolidomide. The expression vector of temozolidomide chemotherapeutic drug and AKT2 short hairpin RNA-AKT2-shRNA was used to treat the tumor of nude mice after tumorigenesis. Then the tumor volume and DNA fragmentation in nude mice were observed and measured by Tunel in situ, and the apoptosis of tumor cells in nude mice after tumorigenesis was calculated and analyzed. The tumor volume and tumor mass in the TMZ AKT2 interference group were 399.86 卤55.26mm ~ (3), 383.81 卤34.01 mm ~ (3), 297.72 卤41.49 mm ~ (3), respectively, and the tumor mass were 1.25 卤0.26 g / g ~ 0.72 卤0.69 卤0.07 g / g ~ (0.69 卤0.07) g 路TMZ AKT2 interference group, respectively. The tumor volume and tumor mass in the tamoxifen group and TMZ negative control group were significantly lower than those in the blank control group, and the tumor mass in the tamoxifen group and the TMZ negative control group were significantly lower than those in the control group (P < 0.01), and the tumor volume in the control group was significantly lower than that in the control group (P < 0.01), and the tumor volume in the control group was significantly lower than that in the control group (P < 0.05). The results of Tunel test showed that the apoptotic index of nude mice in the TMZ-negative control group was significantly higher than that in the control group. The apoptotic index of the nude mice in the TMZ-negative control group was significantly higher than that in the control group. The apoptotic index of the nude mice in the TMZ-negative control group was significantly higher than that in the control group, and the apoptotic index was significantly higher in the AKT2 interference group than in the control group, and the apoptotic index was significantly higher in the TMZ AKT2 interference group than in the control group, and the apoptotic index of the nude mice in the TMZ AKT2 interference group was significantly higher than that in the control group. There was significant difference between temozolidomide group and TMZ negative control group. Conclusion RNA interference with AKT2 can significantly increase the sensitivity of glioblastoma to TMZ chemotherapy in nude mice.
【作者单位】：解放军第411医院神经外科;第二军医大学附属长征医院上海市神经外科研究所;
【基金】：国家自然科学基金资助项目(30930094)
【分类号】：R739.41

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