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目的:探讨KDR启动子驱动双自杀基因体系对荷瘤鼠胃癌的体内抑瘤作用。方法:建立胃癌移植瘤动物模型,当肿瘤直径达0.5cm时,随机分为A组:空白对照,不施加任何处理;B组:注射重组腺病毒AdKDR-CDglyTK与前药5-FC和GCV;C组:仅注射重组腺病毒AdKDR-CDglyTK;D组:仅注射前药5-FC和GCV。治疗过程中绘制肿瘤生长曲线,观察该治疗体系的体内抑瘤效应;通过RT-PCR检测肿瘤组织内融合基因的表达;采用免疫组化行微血管密度检查。结果:接种肿瘤细胞后13d,裸鼠出现右臀区皮下瘤结节。治疗结束后A、B、C、D组间瘤质量差异有统计学意义(F=12 727.42,P=0.000),B组明显缩小。重组腺病毒转基因荷瘤鼠胃癌组织内可检测到CDglyTK融合基因产物的表达。肿瘤组织的MVD值在A、B、C、D组之间差异有统计学意义,F=27.04,P=0.000。结论:KDR启动子驱动双自杀基因体系对裸鼠皮下移植瘤有明显的抑瘤作用,表现为肿瘤的生长抑制和瘤体微血管密度减少等。
Objective: To investigate the antitumor effect of KDR promoter-driven double suicide gene in vivo on tumor-bearing mice gastric cancer. Methods: The animal model of gastric cancer xenografts was established. When the tumor diameter reached 0.5cm, the rats were randomly divided into group A: blank control without any treatment; group B: injection of AdKDR-CDglyTK and prodrug 5-FC and GCV; Group C: only injected recombinant adenovirus AdKDR-CDglyTK; Group D: only prodrugs 5-FC and GCV were injected. The growth curve of the tumor was drawn during the treatment, and the in vivo antitumor effect of the treatment system was observed. The expression of the fusion gene in the tumor tissue was detected by RT-PCR and the microvessel density was examined by immunohistochemistry. Results: On the 13th day after inoculation of tumor cells, the nude mice showed the subcutaneous nodules on the right buttocks. After treatment, the tumor mass of group A, B, C and D was significantly different (F = 12 727.42, P = 0.000), and group B was significantly reduced. The expression of CDglyTK fusion gene product was detected in the gastric cancer tissue of the recombinant adenovirus transdermal tumor bearing mice. The MVD of tumor tissue in group A, B, C and D was significantly different, F = 27.04, P = 0.000. Conclusion: KDR promoter-driven double suicide gene system has obvious anti-tumor effect on subcutaneous xenografts in nude mice, which is manifested as tumor growth inhibition and tumor microvessel density reduction.