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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.
AuthorsSoo Jin Lee, Yasukata Ohashi, Hiroaki Sakurai, Ikuo Saiki
JournalCancer letters (Cancer Lett) Vol. 198 Issue 2 Pg. 169-77 (Aug 20 2003) ISSN: 0304-3835 [Print] Ireland
PMID12957355 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anticarcinogenic Agents
  • Benzoates
  • DNA Primers
  • Drug Implants
  • TAC 101
  • Transcription Factor AP-1
  • Trimethylsilyl Compounds
Topics
  • Animals
  • Anticarcinogenic Agents (administration & dosage, pharmacology)
  • Base Sequence
  • Benzoates (administration & dosage, pharmacology)
  • Carcinoma, Hepatocellular (chemically induced, pathology, prevention & control)
  • Cell Division (drug effects)
  • Cell Movement (drug effects)
  • DNA Primers
  • Disease Models, Animal
  • Drug Implants
  • Liver Neoplasms (chemically induced, pathology, prevention & control, secondary)
  • Mice
  • Mice, Inbred Strains
  • Neoplasm Invasiveness
  • Neoplasm Metastasis (prevention & control)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factor AP-1 (antagonists & inhibitors, drug effects, metabolism)
  • Trimethylsilyl Compounds (administration & dosage, pharmacology)
  • Tumor Cells, Cultured

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