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.