通过不同途径注射可生物发光肿瘤细胞构建膀胱癌全身多器官转移模型

Establishment of metastasis model of bladder cancer by bioluminescence tumor cells via different injection routes

目的探讨通过不同途径注射可生物发光肿瘤细胞构建裸鼠膀胱癌全身多器官转移模型。方法以慢病毒感染膀胱癌细胞株5637获得可稳定表达萤火虫荧光素酶的5637-Luc。分别通过左心室及尾静脉注射构建膀胱癌全身多器官转移模型,并以小动物活体生物发光成像技术观测5637-Luc在裸鼠体内各主要器官的分布,于7天后处死小动物,取出裸鼠内脏观测转移病灶数量并进行对照分析。结果成功构建可生物发光膀胱癌细胞系5637-Luc,生物发光活性与细胞数高度线性相关(R^2=0.995)。经小动物活体生物发光成像观测,通过左心室及尾静脉注射5637-Luc后均可构建膀胱癌全身多器官转移模型,经左心室注射组失败2例,经尾静脉注射组10例全部成功。7天后经左心室注射组平均转移病灶数(11.9±0.83),经尾静脉注射组转移病灶数为(11.8±0.79),注射途径对于肿瘤细胞在裸鼠体内主要器官的分布数量差别无统计学意义(P>0.05)。结论通过不同途径注射可生物发光肿瘤细胞均可成功构建可非侵入性、定量、实时、精确和动态观测的膀胱癌全身多器官转移模型。

Objective To develop metastasis model of bladder cancer by bioluminescence tumor cells via different injection routes. Methods A human transitional cell carcinoma 5637 cell line that stably expresses luciferase by lentivirus infections was generated, and inoculated into the left cardiac ventricle or vena caudalis of immunocompromised mice. Cell distribution was monitored by IVIS200. Analysis of linear regression and t test were used in the study. Results The bioluminescence intensity was linearly correlated with cell counts（R2 = 0.995）. Cancer cells could not be detected in two mice in trans-left cardiac ventricle injection group while cancer cells were detected in all mice in vena caudalis group. The metastasis lesion in thetrans-vena caudalis injection group was（11.8 ±0.79）, metastasis lesion in transleft cardiac ventricle injection group was（11.9 ± 0.83）, there was no significant differences between the tow groups（t = 0.195, P = 0.858）. Conclusion The bioluminescence-based metastasis models developed from different injection routes provide a non-invasive, real-time, quantitative, hypersensitive and dynamic model for preclinical studies.