肝癌人源肿瘤异种移植模型构建及初步应用

发布时间：2018-11-08 18:28

【摘要】：目的建立肝癌人源肿瘤异种移植(patient-derived xenografts,PDX)模型,探讨其在肝癌精准医疗中的作用。方法取临床肝癌新鲜手术切除标本,NCG小鼠皮下接种肿瘤组织建立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。将成功传至第三代的PDX模型制备肿瘤细胞悬液,BALB/c裸鼠皮下接种制作肝癌移植瘤模型15只,成瘤后随机分为5-氟尿嘧啶(5-fluorouracil,5-FU)组、索拉非尼(sorafenib)组和阴性对照组,每组5只。定期监测各组荷瘤小鼠肿瘤体积和重量,根据瘤重计算抑瘤率,评估疗效。结果本研究共建成肝癌PDX模型6例,成功率为33.3%(6/18),模型较好的保持了原发肿瘤的特征。1例PDX模型中,5-FU与索拉非尼组肿瘤抑瘤率分别为63.7%和29.6%,5-FU组抑瘤率比较差异有显著性(P0.05),索拉非尼组抑瘤率比较差异无统计学意义,与临床结果相符。结论肝癌PDX模型保持了患者肿瘤组织的组织形态,可以适用于肝癌患者的精准医疗。
[Abstract]:Objective to establish a human xenotransplantation (patient-derived xenografts,PDX) model of hepatocellular carcinoma (HCC) and to explore its role in accurate treatment of HCC. Methods PDX model was established by subcutaneously inoculating tumor tissue of NCG mice. The morphologic structure of transplanted tumor tissue was compared with that of patient with HE staining. Tumor cell suspensions were prepared from the PDX model successfully transmitted to the third generation. BALB/c nude mice were inoculated subcutaneously to make the transplanted tumor model of liver cancer, and were randomly divided into 5-fluorouraciline 5-FU group after tumorigenesis. Solafenil (sorafenib) group and negative control group, 5 rats in each group. Tumor volume and weight of tumor bearing mice were monitored regularly, tumor inhibition rate was calculated according to tumor weight, and curative effect was evaluated. Results in this study, 6 cases of liver cancer PDX model were established, the success rate was 33.3% (6 / 18). The model maintained the characteristics of primary tumor. The tumor inhibition rates of 5-FU and Solafenil groups were 63.7% and 29.65-FU, respectively (P0.05). There was no significant difference in tumor inhibition rate between Solafenil group and Solafenil group, which was consistent with the clinical results. Conclusion the PDX model of liver cancer can maintain the tissue morphology of tumor tissue and can be applied to the accurate medical treatment of patients with liver cancer.
【作者单位】：中国医学科学院医学实验动物研究所北京协和医学院比较医学中心;首都医科大学附属北京地坛医院;
【基金】：中国医学科学院医学与健康科技创新工程经费资助(2016-I2M-3-019) 中央级公益性科研院所基本科研业务费(2016ZX310032) 协和青年科研基金资助(3332016078)
【分类号】：R-332;R735.7

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