Therapeutic and analysis model of intrahepatic metastasis reflects clinical behavior of hepatocellular carcinoma.
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.
Sawada
Shigeaki
S
Department of Pathogenic Biochemistry, Institute of Natural Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Murakami
Koji
K
Yamaura
Takeshi
T
Mitani
Noriyasu
N
Tsukada
Kazuhiro
K
Saiki
Ikuo
I
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology / Q000556:secondary*; D002945:Cisplatin / Q000494:pharmacology; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary*; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D051379:Mice; D009368:Neoplasm Transplantation; D010647:Phenyl Ethers / Q000494:pharmacology
C414368:N-hydroxy-5-ethoxymethyloxy-2-methyl-4-(4-phenoxybenzoyl)aminopentanamide; D010647:Phenyl Ethers; D004317:Doxorubicin; D020780:Matrix Metalloproteinase 9; D002945:Cisplatin