TAC-101 inhibits intrahepatic metastasis of orthotopically implanted murine hepatocellular carcinoma.
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.
Lee
Soo Jin
SJ
Department of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Ohashi
Yasukata
Y
Sakurai
Hiroaki
H
Saiki
Ikuo
I
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
D016588:Anticarcinogenic Agents; D001565:Benzoates; D017931:DNA Primers; D004343:Drug Implants; C112689:TAC 101; D018808:Transcription Factor AP-1; D014297:Trimethylsilyl Compounds