重组VEGF165-PE38融合基因对裸鼠移植性人胶质瘤血管生成的抑制作用  

A novel VEGF165-PE38 fusion gene for anti-angiogenic therapy in malignant glioma of nude mice model

作　　者：柯以铨[1] 胡昌辰[1] 姜晓丹[1] 王育胜[1] 孙新林[1] 薛杉[1] 张发兵[1] 姚鹏飞[1] 蔡颖谦[1] 

机构地区：[1]南方医科大学珠江医院神经外科,广东神经外科研究所,广东省脑功能修复与再生重点实验室,广州510282

出　　处：《中华神经医学杂志》2009年第12期1203-1206,共4页Chinese Journal of Neuromedicine

基　　金：国家自然科学基金（30901774）;广东省自然科学基金项目（06024442）;广东省科技计划项目（20088030301152）

摘　　要：目的研究血管内皮细胞生长因子（VEGF）和铜绿假单胞菌外毒素A（PE）融合基因的真核表达载体对裸鼠移植性人脑恶性胶质瘤血管生成的影响，探索抗肿瘤血管生成的新方法。方法采用裸鼠背部皮下注射U251细胞建立移植性恶性胶质瘤模型，9d后按随机数字表法将裸鼠分为未治疗组、PBS组、空质粒组、重组质粒组，采用HE染色观察肿瘤组织的形态学变化，免疫组织化学SP法检测胶质纤维酸性蛋白（GFAP）、CD31、PE的表达，分析肿瘤组织的微血管密度（MVD）。结果注射后第16天重组质粒组裸鼠移植瘤体积明显小于其他3组，差异有统计学意义（P〈0．05）；重组质粒组裸鼠移植瘤MVD低于其他3组，差异均有统计学意义（P〈0．05）；重组质粒组裸鼠肿瘤组织PE呈阳性表达，而在空质粒组、PBS组及未治疗组均为阴性表达。结论VEGF165-PE38融合基因的表达产物对人脑恶性胶质瘤有明显的抑制作用，并能抑制肿瘤新生血管生成，可能为一种有效抗肿瘤血管治疗的新策略。Objective To evaluate the anti-angiogenic effect of eukaryotic vector containing human VEGF 165 and truncated pseudomonas exotoxin A （PE38） fusion gene on malignant glioma in nude mice, and explore a novel anti-angiogenic therapy for cancer. Methods The models were established through hypodermic injection of human U251 glioma cells into the nude mice and randomly divided into untreated group, PBS group, pIRES2-EGFP group and pIRES2-VEGF165-PE38-EGFP group on the 9th day. H＆E staining was performed to observe the morphological changes of the glioma tissues; SP immunohistochemistry was employed to detect the expression of GFAP, CD31 and PE; quantitative pathologic image analysis system was used to investigate the microvessel density （MVD） in the tumor tissues. Results At day 16, the pIRES2-VEGF165PE38-EGFP group showed significantly lower tumor volume of mice and significantly decreased MVD than the other three groups （P〈0.05）. Positive expression of PE was shown in the pIRES2-VEGF165PE38-EGFP group, but negative in the other three groups. Conclusion The expression products of VEGF165-PE38 fusion gene can obviously inhibit the growth and angiogenesis of U251 cells in nude mouse flank tumor models, suggesting that it may be a novel therapeutic approach for anti-angiogenic therapy of cancer.

关 键 词：血管内皮细胞生长因子 铜绿假单胞菌外毒素A 融合基因 基因治疗 抗血管治疗 神经胶质瘤 

分 类 号：R686[医药卫生—骨科学]