七甲川菁近红外荧光染料对胃癌原位移植模型的靶向识别  

Tumor targeting of near-infrared fluorescence heptamethine cyanine dye in orthotopically transplanted gastric carcinoma in mice

作　　者：赵勇[1] 张彩勤[1] 赵宁宁[1] 谭邓旭 赵亚[1] 张海[1] 师长宏[1] ZHAO Yong ZHANG Cai-qin ZHAO Ning-ning TAN Deng-xu ZHAO Ya ZHANG Hai SHI Chang-hong(Laboratory Animal Center, the Fourth Military Medical University, Xi＇ an 710032, China)

机构地区：[1]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》2016年第6期567-571,578,共6页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金项目(31572340);陕西省统筹科技资源项目(2016FWPT-02)

摘　　要：目的研究七甲川菁近红外荧光(NIRF)染料在胃癌原位移植模型活体成像中的应用效果。方法将标记荧光酶素的人胃癌细胞系Hep G2原位移植裸鼠建立肿瘤模型,同时诱发制备胃溃疡模型;对上述模型分别采用生物发光成像和NIRF成像,观察胃癌组织对近红外荧光染料的吸收;探索缺氧和阴离子转运肽(OATP)对胃癌组织吸收NIRF染料的影响,明确NIRF染料靶向识别肿瘤细胞的特异性。结果 NIRF信号与生物发光信号在胃癌原位移植模型活体成像中具有较好的相关性。胃癌组织部位可获得较强的NIRF荧光信号,而胃溃疡部位未检测到荧光信号。缺氧能够增强胃癌细胞对NIRF染料的吸收,而阴离子转运肽特异性抑制剂磺溴酞钠(BSP)能够显著降低肿瘤细胞对NIRF染料的吸收。结论七甲川菁近红外荧光染料能够靶向识别胃癌原位移植模型。Objective To determine the target recognition ability of the near-infrared fluorescence（ NIRF） heptamethine cyanine dye in mouse models of orthotopically transplanted gastric carcinoma with optical imaging. Methods The orthotopically transplanted model of gastric carcinoma was established by implantation of luciferase-tagged-Hep G2 cells into the stomach in nude mice,and gastric ulcer model was induced by absolute ethanol. Both bioluminescence（ BIL） signal and NIRF signal in those two animal models were observed with optical imaging respectively,and the absorption of NIRF dye in gastric carcinoma tissues was determined. We further explored the effect of hypoxia and OATP on the absorption of the NIRF dye in gastric carcinoma tissues. The specific targeting ability of NIRF dye to tumor cells was evaluated. Result A good positive correlation was observed between NIRF signal and BIL signal（ R^2= 0. 995）. Strong NIRF signal was observed in gastric carcinoma region,but no signal was found in the gastric ulcer model. Moreover,hypoxia further promoted the uptake of NIRF dye in gastric carcinoma,but OATP specific inhibitor BSP significantly reduced the absorption of NIRF dye in tumor cells. Conclusions The NIRF heptamethine cyanine dye can be applied to identify the orthotopically transplanted gastric carcinoma in nude mouse models.

关 键 词：近红外荧光染料 胃癌 肿瘤原位移植模型 裸鼠 

分 类 号：Q95-33[生物学—动物学]