Sawada Shigeaki, Murakami Koji, Yamaura Takeshi, Mitani Noriyasu, Tsukada Kazuhiro, Saiki Ikuo
Department of Pathogenic Biochemistry, Institute of Natural Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Jpn J Cancer Res. 2002 Feb;93(2):190-7. doi: 10.1111/j.1349-7006.2002.tb01258.x.
This study was designed to establish an intrahepatic metastasis model to investigate the biology and therapy of hepatocellular carcinoma (HCC) in mice. A fragment of mouse HCC tumor CBO140C12 was orthotopically implanted into the mouse liver. The number of intrahepatic metastatic colonies and the volume of the implanted tumor increased in a time-dependent manner. At 28 days after fragment implantation, all mice showed intrahepatic metastasis. Intravenous administrations of cisplatin and doxorubicin at 7 and 21 days after the implantation significantly suppressed the growth of the primary tumor nodule, but tended to inhibit intrahepatic metastasis. However, a marked decrease of body weight was observed during the experiment. On the other hand, an inhibitor of matrix metalloproteinases (MMPs), ONO-4817, decreased the gelatinase activity of MMP-9 secreted by CBO140C12 cells, and significantly reduced the number of colonies of intrahepatic metastasis when administered orally. Our established model, which is focused on intrahepatic metastasis, is suitable for evaluating the therapeutic effect of HCC and for analyzing intrahepatic metastasis, because this model reflects the clinical features of HCC and all the steps of tumor metastasis.
本研究旨在建立一种肝内转移模型，以研究小鼠肝细胞癌（HCC）的生物学特性及治疗方法。将小鼠肝癌肿瘤CBO140C12的一个片段原位植入小鼠肝脏。肝内转移瘤集落数量和植入肿瘤的体积呈时间依赖性增加。片段植入后28天，所有小鼠均出现肝内转移。植入后7天和21天静脉注射顺铂和阿霉素可显著抑制原发性肿瘤结节的生长，但有抑制肝内转移的趋势。然而，实验期间观察到体重显著下降。另一方面，基质金属蛋白酶（MMPs）抑制剂ONO - 4817可降低CBO140C12细胞分泌的MMP - 9的明胶酶活性，口服给药时可显著减少肝内转移瘤集落数量。我们建立的专注于肝内转移的模型适用于评估HCC的治疗效果和分析肝内转移，因为该模型反映了HCC的临床特征及肿瘤转移的所有步骤。
