非小细胞肺癌病人源性NOD/SCID小鼠和BALB/c裸鼠移植瘤模型的建立及比较

Comparison of patientderived non-small cell lung cancer xenegrafts models in NOD/SCID and nude mice

目的:构建人非小细胞肺癌的NOD/SCID小鼠和BALB/c裸鼠移植瘤模型,并探讨移植瘤成瘤性与小鼠品系间的关系,为后续建立优良的动物模型奠定基础。方法:取手术切除获得的23例非小细胞肺癌组织,1 h内移植于NOD/SCID小鼠或BALB/c裸鼠皮下,观察移植瘤成瘤情况,测量移植瘤体积,绘制生长曲线图,计算成瘤率、成瘤潜伏时间和成瘤时间,分析并比较移植成瘤组和未成瘤组所对应患者的相关临床病理指标,并取移植成瘤组和所对应患者的组织标本进行病理学分析。结果:NOD/SCID小鼠皮下移植瘤模型成瘤率(55.6%),BALB/c裸鼠皮下移植瘤模型(20%),两者间差异无统计学意义(P>0.05),但前者的成瘤潜伏时间和成瘤时间均短于后者(P<0.05)。患者相关临床病理指标中鳞癌、TNM分期和淋巴结转移情况与移植瘤成瘤建模无明显相关(P=0.109、0.153、0.077),NOD/SCID小鼠和BALB/c裸鼠皮下移植瘤模型均能保持病人肺癌肿瘤组织的形态学特征。结论:成功构建了NOD/SCID小鼠和BALB/c裸鼠皮下移植瘤模型,NOD/SCID小鼠更适宜用于肺癌病人源性皮下移植瘤模型的建立,非小细胞肺癌移植瘤模型的建立为进行体外抗肿瘤药物的筛选提供了良好的研究工具。

OBJECTIVE:To establish patient-derived non-small cell lung cancer xenegraft models in NOD/SCID or nude mice,and to compare the tumor-forming rates between these mice.METHODS:Non-small cell lung cancer tissues were collected from 23 patients who underwent surgical resection at the Department of Thoracic Surgery of Beijing Chest Hospital from July 2016 to December 2016.Non-small cell lung cancer tissues were subcutaneously implanted into NOD/SCID mice or BALB/c nude mice within 1 hour after surgical resection.Growth processes of the xenotransplanted tumors were observed,the tumor volumes were measured and the growth curves of the xenotransplanted tumors were plotted.The tumor-forming rates,the tumor latent time and the tumor formatting time were calculated.Then,comparison was made on morphology of patient-derived tumor xenegraft tissue and corresponding primary tumor tissue,and the related patients clinical pathological index of two groups,that could form xenegraft tumor group and couldn't form xenergraft tumor group.RESULTS:Xenegrafts were successfully established(55.6%)in NOD/SCID and(20%)nude mice.The tumor-forming rates of NOD/SCID mice models were higher than the nude mice models,and the tumor latent time(37 d,60 d,P=0.002)and the tumor formatting time(79 d,110 d,P=0.002)had significant differences.Tumor factors might associate with engraftment included squamous histology,TNM stage and the lymph node metastasis.Both mice models could keep the morphology of patient-derived tumor xenegraft tissues.CONCLUSION:The xenotransplantation models of patient-derived non-small cell lung cancer in both NOD/SCID mice and nude mice were successfully established.In comparison with the BALB/c nude mice model,the tumor-forming rates of the NOD/SCID mice model was higher,the tumor latent times and the tumor formatting times were shorter,suggesting that the NOD/SICD mice model was more suitable for the establishment of patient-derived NSCLC xenegraft model.