TAC-101 inhibits intrahepatic metastasis of orthotopically implanted murine hepatocellular carcinoma

Soo Jin Lee; Yasukata Ohashi; Hiroaki Sakurai; Ikuo Saiki

doi:10.1016/s0304-3835(03)00306-9

TAC-101 inhibits intrahepatic metastasis of orthotopically implanted murine hepatocellular carcinoma

Cancer Lett. 2003 Aug 20;198(2):169-77. doi: 10.1016/s0304-3835(03)00306-9.

Authors

Soo Jin Lee¹, Yasukata Ohashi, Hiroaki Sakurai, Ikuo Saiki

Affiliation

¹ Department of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.

PMID: 12957355
DOI: 10.1016/s0304-3835(03)00306-9

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anticarcinogenic Agents / administration & dosage
Anticarcinogenic Agents / pharmacology*
Base Sequence
Benzoates / administration & dosage
Benzoates / pharmacology*
Carcinoma, Hepatocellular / chemically induced
Carcinoma, Hepatocellular / pathology
Carcinoma, Hepatocellular / prevention & control*
Cell Division / drug effects
Cell Movement / drug effects
DNA Primers
Disease Models, Animal
Drug Implants
Liver Neoplasms / chemically induced
Liver Neoplasms / pathology
Liver Neoplasms / prevention & control*
Liver Neoplasms / secondary*
Mice
Mice, Inbred Strains
Neoplasm Invasiveness
Neoplasm Metastasis / prevention & control*
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factor AP-1 / antagonists & inhibitors
Transcription Factor AP-1 / drug effects
Transcription Factor AP-1 / metabolism
Trimethylsilyl Compounds / administration & dosage
Trimethylsilyl Compounds / pharmacology*
Tumor Cells, Cultured

Substances

Anticarcinogenic Agents
Benzoates
DNA Primers
Drug Implants
TAC 101
Transcription Factor AP-1
Trimethylsilyl Compounds