新型血管生成抑制融合基因ENDO-VGEI151对胃癌抑制作用的比较评价.DOCVIP

临床医学论文-新型血管生成抑制融合基因ENDO-VGEI151对胃癌抑制作用的比较评价 　【摘要】? 目的? 比较内皮细胞抑制素－血管内皮细胞生长抑制因子151（ENDO-VGEI151）融合基因与ENDO和VGEI151单基因及联合基因治疗对胃癌的抑制作用，评价融合基因的治疗价值。方法? 建立荷胃癌裸鼠模型，48只荷瘤裸鼠随机分成6组：PBS组、Ad LacZ组、Ad ENDO-VGEI151组、Ad ENDO组、Ad VGEI151组及Ad ENDO＋Ad VGEI151联合组，每组8只。接种后第5天起在瘤体内和瘤周注射滴度为2×109pfu/ml的相应重组腺病毒500μl，联合基因组用250μl Ad ENDO+250μl Ad VGEI151，隔日1次，共10次。末次注射24h后处死动物，测量种植瘤体积和瘤重、抑瘤率、肿瘤微血管密度（MVD）、肿瘤细胞凋亡指数（AI）、血管内皮细胞生长因子（VEGF165）表达指数；流式细胞仪（FCM）和电镜观察检测癌细胞凋亡情况。结果? 融合基因组、ENDO组、VGEI151组和联合基因组种植瘤体积分别为（391.67±146.43）mm3、（1568.48±198.23）mm3、（1832.85±178.82）mm3、（822.86±163.41）mm3；抑瘤率为88.11%、52.39%、44.37%、75.02%；MVD分别为（11.50±3.42）、（35.18±4.15）、（34.37±2.72）、（21.49±2.74）；AI分别为（61.39±6.36）%、（35.84±6.52）%、（39.69±5.24）%、（45.50±7.64）%；VEGF165表达指数为（31.58±4.06）%、（58.74±7.64）%、（53.25±4.42）%、（43.15±4.57）%；FCM分析凋亡细胞比例分别为（16.04±4.07）%、（3.15±1.17）%、（2.83±0.86）%、（7.15±2.15）%。融合基因与两单基因或联合基因组相比，组间抑瘤率、MVD，AI及VEGF165表达差异均有显著性（P＜0.01）。结论? 融和基因ENDO-VGEI151通过抑制血管内皮细胞增殖，下调癌细胞表达VEGF165，协同抑制肿瘤内新生血管形成，诱导癌细胞凋亡，其疗效明显优于单基因和联合基因治疗，值得深入研究。 　　【关键词】? 胃癌；基因治疗；血管内皮细胞生长抑制因子151 　　Comparative evaluation of inhibitory effects of endostatin-vascular endothelial growth inhibitor151 chimeric gene therapy on gastric carcinoma 　　【Abstract】? Objective? To compare the inhibitory effects of endostatin-vascular endothelial growth inhibitor151 (ENDO-VGEI151) chimeric gene on gastric carcinoma with endostatin or VGEI151 gene alone and combination of the endostatin and VGEI151.Methods?The recombinant adenovirus containing ENDO-VGEI151 chimeric gene, ENDO gene and VGEI151 gene was constructed.48 nude mice were randomly divided into 6 groups which were subjected to the injection of PBS,Ad LacZ,Ad ENDO-VGEI151,Ad ENDO,Ad VGEI151 and Ad ENDO+Ad VGEI151 respectively.The injection was administered 10 times at an interval of 1 day.Twenty-five days after implantation, tumor size and weight,inhibition rate,intratumoral microvessel density(MVD),apoptotic index（AI）,and VEGF165 expression index were evaluated respectively after the mice were sacrificed.