肝癌人源肿瘤异种移植模型构建及初步应用

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。

Establishment and application of a patient derived xenograft mouse model of liver cancer

Objective To establish a patient-derived xenografts (PDX) mouse model of liver cancer (LC) and to explore its role in precision medicine. Methods PDX model was established by subcutaneous implantation of tumor tissues in NCG mice. The morphological structure of tumor tissue was exaimed using HE staining. Fifteen BALB/c nude mice were subcutaneously inoculated with tumor cell suspension from the PDX models. The xenograft mice were randomly divided into 5-fluorouracil (5-FU) group, sorafenib group and negative control group. The tumor volume and body weight of the tumor-bearing mice were measured regularly, the tumor inhibition rate was calculated and the curative effect was evaluated. Results The success rate was 33.3% (6/18) in the establishment of liver cancer PDX mouse model, and the model well retained the characteristics of the primary tumor. In one case of PDX mouse model, the tumor inhibition rates of 5-FU and sorafenib group were 63.7% and 29.6%, with a statistically significant differece between them (P<0.05), and there was no significant difference between the sorafenib group and negative control group, consistent with clinical observation. Conclusions The PDX mouse model of liver cancer can maintain the histological structure of primary tumor, and can be applied to precision medicine for patients with liver cancer.