裸鼠人肝癌原位移植转移模型的生长特性及转移潜能

Growth pattern and metastatic behaviour of orthotopically metastatic model of human hepatocellular carcinoma in nude mice

为了研究癌转移的机理和筛选抗转移治疗因子，用原位移植方法建立了裸鼠人肝癌高转移模型ＬＣＩ－Ｄ２０。对该模型的体内生长与转移规律、宿主血清甲胎蛋白（ＡＦＰ）水平，不同植入环境对转移能力的影响进行了观察，并检测了其细胞形态学、染色体核型和ＤＮＡ含量。结果：ＬＣＩ－Ｄ２０模型传代１２次，移植生长率为１００％，宿主生存期４０天，传代周期２０天。移植生长曲线呈直线递增，倍增时间则呈直线递减。转移初始于肝内，３周后发生淋巴结与肺转移，转移率１００％（７０／７０）。皮下与腹腔接种后，仍表现高转移特性，肺转移分别为７０％（７／１０）和１００％（１０／１０）。宿主血清ＡＦＰ水平呈曲线递增，第５周达最高值（７９７．５μｇ／Ｌ）。光镜与电镜观察示人肝癌细胞特征。染色体与ＤＮＡ含量分析示异倍体核型。结果表明：由原位移植方法建立的裸鼠人肝癌转移模型，能在人体外模拟人肝癌转移的自然过程，是一株可供研究人肝癌转移问题的较为理想的模型。

Growth pattern,metastatic behaviour and serial alph-a-fetoprotein(AFP)level of highly metastatic model of human hepatocellular carcinoma in nude mice(LCI-D20),which constructed by using orthotopic implantation of histologically intact patient specimens,were studied by implanting into the liver, subcutis andperitoneum of nude mice.Pathologic(by light and electronmicroscopic examination)and biologic(chromosome karyotype and DNA contents by flow cytometry)characteristics of LCI-D20 were also observed.The results showed that transplantability of LCI-D20 was 100% in 12 generations(passage time:20 days)and all of these mice implanted tumors died within 40 days after transplantation due to serious metastasis.After LCI-D20 implanted into the liver of nude mice,growing implant-tumors in progress were negatively related to their double time during animal survival.LCI-D20 maintained 100%(70/70) metastatic rate in nude mice that showed early intrahepatic metastasis and late lymphatic and pulmonary metastasis.The high metastatic potentials of LCI-D20 tumor cells were kept in subcutis and peritoneum (70%,100% respectively). The increase of the serial AFP secreting from the tumor cells was correlated with the implantation tumor growth rate(797.5μg/L/5th week).The data from histological and electronmicroscopic findings,chromosome karyotype and DNA content analysis of the tumor cells revealed characteristics of human hepatocellular carcinoma.The results indicated that LCI-D20 exhibited the variety of clinical behaviours seen in hepatoma patients and it could be a useful model for investigating the metastasis mechanism of human hepatoma and anti-metastasis therapy.