am-555s and Neoplasm-Metastasis

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.

Topics: Animals; Anticarcinogenic Agents; Base Sequence; Benzoates; Carcinoma, Hepatocellular; Cell Division; Cell Movement; Disease Models, Animal; DNA Primers; Drug Implants; Liver Neoplasms; Mice; Mice, Inbred Strains; Neoplasm Invasiveness; Neoplasm Metastasis; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factor AP-1; Trimethylsilyl Compounds; Tumor Cells, Cultured