体内示踪技术评价噬菌体展示肽GX1特异靶向胃癌新生血管  

Specific targeting of the vasculature of gastric cancer by a phage displayed peptide GX1using trace technique in vivo

作　　者：惠晓丽[1] 梁树辉[2] 刘洋[2] 刘惊涛[3] 吴开春[2] 

机构地区：[1]西安交通大学第一附属医院内分泌科干部病区,陕西西安710061 [2]第四军医大学西京消化病医院肿瘤生物学国家重点实验室,陕西西安710032 [3]中国人民解放军第451医院核医学科,陕西西安710054

出　　处：《现代肿瘤医学》2015年第14期1940-1943,共4页Journal of Modern Oncology

基　　金：国家自然科学基金重大项目(编号:81090270;81090273);国家自然科学基金项目(编号:30900704);国家科技重大专项"重大新药创制"专题(编号:2009ZX09103-667);国家高技术研究发展计划(863计划)项目(编号:2006AA022103);陕西省科技攻关计划项目(编号:2013K12-09-03);陕西省自然科学基金项目(编号:2014JM2-8184)

摘　　要：目的:评价噬菌体展示肽GX1与胃癌新生血管结合的特异性及体内靶向性。方法:化学合成BioGX1展示肽;构建人胃癌移植瘤裸鼠模型,A组将Bio-GX1展示肽经尾静脉注入荷瘤小鼠体内,分别于体内循环8h、12h、18h、24h时处死裸鼠,B组将GX1噬菌体经尾静脉注入荷瘤小鼠体内,于体内循环8min时处死裸鼠,免疫荧光方法检测GX1噬菌体及展示肽与胃癌血管体内结合特异性及靶向性;构建小鼠肾包膜下胃癌移植瘤模型,分别于移植瘤术后第5天、第10天经尾静脉注入Bio-GX1展示肽,体内循环8h处死小鼠,免疫荧光方法检测GX1与胃癌血管体内结合的特异性及靶向性。结果:GX1展示肽体内循环8-24h,GX1噬菌体体内循环8min,可特异靶向人胃癌移植瘤裸鼠胃癌组织血管,而与肝、心、脾、肾(脑)、肺、肌肉组织等对照组织血管未见明显结合;GX1展示肽体内循环8h,可特异靶向小鼠肾包膜下胃癌移植瘤模型肿瘤血管,与对照组织血管未见明显结合。结论:GX1噬菌体及展示肽均可在体内特异靶向胃癌血管,具有体内胃癌血管靶向性,可作为胃癌血管靶向治疗及诊断的有效候选分子。Objective：To evaluate the specific binding ability and targeting ability of phage displayed peptide GX1 to the vasculature of gastric cancer by trace technique in vivo.Methods：Bio-GX1 peptide was synthesized by chemosynthesis.Group A：Bio-GX1 peptide was injected into the tail vein of nude mice bearing tumor xenografts of human gastric cancer which were then kept for 8h,12h,18h,and 24h.Group B：GX1 phage was injected into the tail vein of nude mice bearing tumor xenografts of human gastric cancer which were then kept for 8min.Then immunofluorescence was done in Group A and B to evaluate the the specific binding ability and targeting ability of GX1 phage and peptide to the vasculature of gastric cancer.Bio-GX1 peptide was injected into the tail vein of immunosuppressed mice model with human gastric cancer xenograft by subrenal capsule assay at 5 and 10day,and then was kept for 8h,immunofluorescence was done to evaluate the specific binding ability and targeting ability of GX1 peptide to the vasculature of gastric cancer.Results：GX1 peptide or phage could target to the tumor vasculature of gastric cancer xenografts after being kept in vivo for 8-24h or 8min respectively in contrast to no binding to the vasculature of normal liver,heart,spleen,lung,kidney,muscle,etc.GX1 peptide could target to the tumor vasculature of immunosuppressed mice model with human gastric cancer xenograft by subrenal capsule assay at 5 and 10day in contrast to no binding to the vasculature of normal controlled tissues.Conclusion：GX1 peptide or phage own the ability of specific targeting to the tumor vasculature of gastric cancer in vivo,and could be selected for effective angiogenesis targeting peptide receptor diagnosis and therapy in gastric cancer.

关 键 词：胃癌 血管靶向 噬菌体展示肽 GX1 体内示踪技术 

分 类 号：R730[医药卫生—肿瘤] R735.2[医药卫生—临床医学]