近红外荧光染料在胃癌人源性肿瘤组织异种移植模型研究中的应用  

Application of near infrared fluorescent dye in the study of patient-derived gastric cancer xenograft nude mouse models

作　　者：赵宁宁[1,2] 张彩勤[2] 赵勇[2] 杨丽[1,2] 张海[2] 刘漪沦[1] 师长宏[1,2] 

机构地区：[1]成都医学院,成都610500 [2]第四军医大学实验动物中心,西安710032

出　　处：《中国实验动物学报》2015年第6期643-647,共5页Acta Laboratorium Animalis Scientia Sinica

基　　金：军队实验动物专项课题资助(SYDW2014-002);国家自然科学基金项目(31572340)

摘　　要：目的建立胃癌人源性肿瘤组织异种移植(patient-derived tumor xenograft,PDX)裸鼠模型,探讨近红外荧光(near infrared fluorescence,NIRF)染料IR-783在胃癌PDX模型活体成像研究中的应用。方法取临床胃癌新鲜手术切除标本,裸鼠肾包膜移植建立PDX模型,HE染色比较移植肿瘤组织与患者肿瘤组织形态结构的一致性。将移植肿瘤组织裸鼠皮下接种,20 d后,荷瘤小鼠腹腔注射NIRF染料IR-783(每只10 nmol/L),活体成像连续测定肿瘤部位近红外荧光强度并分析肿瘤体积与荧光强度的相关性;免疫组织化学检测移植肿瘤组织中HIF1α与OATP1B3的表达强度。结果成功建立了3个人胃癌PDX模型,移植肿瘤组织较好的保持了原发肿瘤的特征,NIRF活体成像早期检测到肾包膜部位荧光信号。PDX模型中肿瘤体积与荧光强度的相关性均在98%以上。移植肿瘤组织中HIF1α与OATP1B3表达呈强阳性。结论 NIRF染料IR-783可在PDX模型肿瘤部位特异性聚集,用于PDX模型的早期检测,这种肿瘤靶向性可能与HIF1α和OATP1B3的表达相关。Objective To establish a patient-derived gastric cancer xenograft（ PDX） model in nude mice and to investigate the application of near infrared fluorescent（ NIRF） dye IR-783 in in vivo imaging of gastric cancer xenograft models. Methods Fresh human gastric cancer tissue was taken and transplanted into the subrenal capsule of nude mice to establish the xenograft model. When the transplanted tumors grew,took part of the tumor tissue to do HE staining and compare the structural characteristics with the primary tumor. Another portion of the tumor was xenografted into nude mice subcutaneously. Twenty days later,the tumor-bearing mice were injected intraperitoneally with IR-783 dye（ 10μM） in a dose of 100 mg /20 g. The intensity of the tumor image was monitored by optical NIRF imaging. The correction between tumor volume and fluorescence intensity was analyzed. Finally,the expression of OATP1B3 and HIF1α in the xenografted tumor tissue was detected by immunohistochemistry. Results We successfully established three patient-derived xenograft（ PDH） models of human gastric cancer. The transplanted tumor tissues maintained the histological characteristics of the primary tumor well. NIRF signal can be detec ted in subrenal capsule of the xenografted nude mice. The correlation between tumor size and fluorescence intensity in the PDX models reached higher than 98%. Strong positive expressions of HIF1α andOATP1B3 in the tumor tissues were detected. Conclusions NIRF dye IR-783 can be specifically accumulated at the tumor site,therefore,can be used to detect PDX in vivo early. The tumor targeting property may be related to the expression of OATP1B3 and HIF1α.

关 键 词：人源性肿瘤组织异种移植模型 近红外荧光染料 低氧诱导因子-1 有机阴离子转运多肽1B3 

分 类 号：Q95-33[生物学—动物学]