title: TAC-101 inhibits intrahepatic metastasis of orthotopically implanted murine hepatocellular carcinoma.
abstract: The anti-metastatic effect of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid (TAC-101) was investigated using our established intrahepatic metastasis model. Orthotopic implantation of a fragment of CBO140C12 hepatoma into the liver resulted in the formation of a solitary tumor nodule and its intrahepatic metastasis. Daily oral administration of TAC-101 at a dose of 8 mg/kg resulted in a significant inhibition of intrahepatic metastasis, but did not affect the growth of the tumor at the implanted site. The down-regulation of transcriptional anti-activator protein-1 (AP-1) activity by TAC-101 paralleled the inhibition of cell invasion and migration through the repression of expression of the mRNAs for urokinase-type plasminogen activator (u-PA) and its receptor (u-PAR). These findings suggest that TAC-101 may improve therapeutic efficacy for liver cancer patients to prevent intrahepatic metastasis.
authors.affiliation: Department of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Yasukata
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sakurai
authors.forename: Ikuo
authors.initials: I
authors.lastname: Saiki
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001483:Base Sequence; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D017931:DNA Primers; D004195:Disease Models, Animal; D004343:Drug Implants; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control* / Q000556:secondary*; D051379:Mice; D008815:Mice, Inbred Strains; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D014297:Trimethylsilyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D016588:Anticarcinogenic Agents; D001565:Benzoates; D017931:DNA Primers; D004343:Drug Implants; C112689:TAC 101; D018808:Transcription Factor AP-1; D014297:Trimethylsilyl Compounds