靶向性近红外荧光染料在肝癌模型研究中的应用

发布时间：2018-10-18 13:19

【摘要】：目的探讨七甲川花菁近红外荧光(near-infrared fluorescence,NIRF)染料IR-783在肝癌模型影像研究中的应用,分析该染料靶向肿瘤细胞的分子机制。方法将标记荧光素酶的人肝癌细胞Hep G2皮下接种裸鼠,测试肿瘤发生部位生物发光(bioluminescence,BIL)信号与NIRF信号的相关性。采用肾包膜下移植的方式建立人肝癌裸鼠移植(patient-derived xenograft,PDX)模型,观察IR-783对肿瘤边界的识别能力;苏木素-伊红染色(hematoxylin-eosin staining,HE staining)确认肿瘤发生的部位,免疫组织化学(Immunohistochemistry,IHC)检测肝癌肿瘤组织中CEA、AFP、HIF1α和OATP3A1的表达;使用线粒体示踪剂(Mito Tracker)和溶酶体示踪剂(Lyso Tracker)确认NIRF染料在肝癌细胞中的结合部位;测试IR-783对正常肝细胞中混合培养的肝癌细胞鉴别能力。结果人肝癌裸鼠皮下移植瘤BIL与NIRF强度具有较好的相关性;NIRF染料IR-783能够清晰识别肾包膜移植肝癌肿瘤边缘;IHC染色显示肿瘤组织中CEA、AFP、HIF1α和OATP3A1均高表达;IR-783主要结合在肿瘤细胞的线粒体与溶酶体中;标记GFP的人肝癌细胞Hep G2能够被IR-783特异性识别。结论 IR-783是一种具有肿瘤靶向和成像特征的新型近红外荧光染料,其靶向性可能与肝癌组织中HIF1α和OATP3A1的高表达相关。
[Abstract]:Objective to investigate the application of heptachuan cyanine near infrared fluorescence (near-infrared fluorescence,NIRF) dye IR-783 in the study of liver cancer model and to analyze the molecular mechanism of the dye targeting tumor cells. Methods Hep G2 cells labeled with luciferase were subcutaneously inoculated into nude mice and the correlation between bioluminescence (bioluminescence,BIL) signal and NIRF signal in tumor site was measured. A nude mouse model of human hepatocellular carcinoma (patient-derived xenograft,PDX) was established by subcapsular transplantation to observe the ability of IR-783 to recognize tumor boundary. Hematoxylin eosin staining (hematoxylin-eosin staining,HE staining) was used to identify the location of tumor. Immunohistochemistry (Immunohistochemistry,IHC) was used to detect the expression of CEA,AFP,HIF1 伪 and OATP3A1 in hepatocellular carcinoma, and mitochondrial tracer (Mito Tracker) and lysosomal tracer (Lyso Tracker) were used to identify the binding sites of NIRF dye in HCC cells. The ability of IR-783 to differentiate hepatoma cells from normal hepatocytes was tested. Results there was a good correlation between BIL and NIRF intensity in nude mice with human hepatocellular carcinoma, NIRF dye IR-783 could clearly identify the tumor edge of renal capsule transplantation liver cancer, IHC staining showed high expression of CEA,AFP,HIF1 伪 and OATP3A1 in tumor tissue, IR-783 was mainly bound to tumor tissue. Mitochondria and lysosomes of tumor cells; Human hepatoma cell Hep G2 labeled with GFP can be specifically recognized by IR-783. Conclusion IR-783 is a novel near infrared fluorescent dye with tumor targeting and imaging characteristics. Its targeting may be related to the high expression of HIF1 伪 and OATP3A1 in HCC tissues.
【作者单位】：第四军医大学实验动物中心;
【基金】：国家自然科学基金项目(31572340) 军队实验动物专项课题(SYDW2014-002)
【分类号】：R735.7

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