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目的构建并实验评价转染与转录双重靶向性基因治疗系统对垂体腺瘤的治疗作用。方法构建GE7基因导入系统介导的生长激素启动子调控的基因治疗系统,通过对垂体生长激素腺瘤GH3细胞的体外实验,以及垂体腺瘤裸鼠模型的体内实验,观察此系统用于垂体腺瘤基因治疗的可能性和靶向性。结果成功构建双重靶向性基因治疗系统;基因转染后,GH3细胞可检测到HSVTK蛋白,对照细胞为阴性;在此基础上予以GCV(4mg/L),GH3细胞存活率平均为106%,相同条件下,U2OS、HO8910PM的存活率分别为829%和935%(P<001);裸鼠皮下种植肿瘤经基因治疗后,治疗组肿瘤体积明显缩小(168mm3±17mm3),各对照组肿瘤体积均有不同程度的增大(P<001);治疗组裸鼠的生存期也较对照组明显延长(平均123d和40d,P<001)。结论GE7转染的生长激素启动子调控的基因治疗有望成为垂体腺瘤的靶向性治疗策略。
Objective To construct and experimentally evaluate the therapeutic effect of transfection and transcriptional dual-targeted gene therapy system on pituitary adenoma. METHODS: The gene therapy system for the regulation of growth hormone promoter mediated by the GE7 gene introduction system was constructed. In vitro experiments of pituitary adenoma GH3 cells and in vivo experiments of pituitary adenoma in nude mice model were observed for pituitary gland Tumor gene therapy possibilities and targeting. Results Double-targeting gene therapy system was successfully constructed. HSVTK protein was detected in GH3 cells and negative in control cells after gene transfection. On the basis of GCV (4 mg / L), the average survival rate of GH3 cells was 106% Under the same conditions, the survival rates of U2OS and HO8910PM were 829% and 935%, respectively (P <001). After gene therapy, the tumor volume of the treated group was significantly reduced (168mm3 ± 17mm3), and the tumor volume (P <001). The survival time of the nude mice in the treatment group was significantly longer than that in the control group (mean 123d and 40d, P <001). Conclusion The gene therapy controlled by growth hormone promoter transduced by GE7 is expected to become a targeted therapeutic strategy for pituitary adenoma.