保持人肝癌生物学特性的人肝癌组织裸鼠肝内种植模型的建立

The establishment of a nude mouse model of intrahepatic implantation of human liver carcinoma tissue with unchanged tumor biologic features

目的建立保持人肝癌特性的裸鼠肝内种植模型。方法用新鲜的人肝癌组织种植于裸鼠肝脏 ;B型超声观察种植瘤的体积变化 ;解剖及显微镜下观察种植瘤的转移情况及组织细胞病理特征 ;免疫组化和RT PCR法测定其MDR1和LRP ;SPECT检测荷瘤鼠骨转移情况。结果第 1代种植 8只裸鼠 ,2w后种植瘤 10 0 %存活 ,并分泌AFP ;8～ 10w内有肝内转移的占 75 0 % ,骨转移占37 5 % ,10w末处死模型鼠 ,有肺转移的占 37 5 % ;种植瘤的病理特征与瘤源患者肝癌一致 ;种植瘤与原肿瘤源组织MDR1、LRP蛋白及其mRNA表达差异均无显著性 (P >0 0 5 )。第 2和第 3代模型鼠各 8只 ,种植后 2w 10 0 %存活 ;10～ 14w裸鼠出现衰竭症状后其肝内、肺和骨均有转移。结论该模型保持了人肝癌生物学特性 ,可用于体内研究人肝癌的模型。

Objective To establish a nude mouse model of intrahepatic implantation of human hepatocellular carcinoma(HCC) tissues with unchanged tumor biologic features. MethodsHistologically intact fresh HCC specimens were implanted in the liver of nude mouse (BALB/c nu/nu). The pathology and metastasis were observed,bone metastasis was detected by SPECT. MDR1 and LRP proteins and mRNA expressions were investigated by immunohistochemistry (SP) and RT-PCR respectively. ResultsSpecimens from a HCC patient were implanted into 8 nude mice,with survival rate of 100% and all excreted AFP after 2 weeks. The spontaneous metastatic rates of liver and bone were 75.0% and 37.5% respectively in 8 w～10 w ,and 37.5% of lung metastasis were found after 10 w. The MDR1 and LRP proteins and mRNA expressions from the patient and that from the nude mouse model were similar ( P >0.05). Second and third generation of the implanted tumor were obtained in 8 nude mice respectively,and all transplanted tumors survived. Liver,bone and lung metastasis were found in 100% of nude mice between 10 w～14 w. [WT5”HZ] Conclusions This nude mouse HCC model holds the biologic features of human HCC and serves the purpose of in vivo study investigation .