TAC-101 (4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid) inhibits spontaneous mediastinal lymph node metastasis produced by orthotopic implantation of Lewis lung carcinoma.

Abstract

The anti-tumor and anti-metastatic effects of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid (TAC-101) were investigated using our established lung cancer model. Orthotopic implantation of Lewis lung carcinoma (LLC) cells into the lung parenchyma produced a solitary tumor nodule in the lung followed by mediastinal lymph node metastasis. Daily oral administration of TAC-101 at doses ranging from 4 to 16 mg/kg resulted in a significant inhibition of lymphatic metastasis (inhibition rate=57 to 76%), while only the dose of 16 mg/kg significantly inhibited tumor growth at the implanted sites (inhibition rate=46%). Combined treatment with cis-diamminedichloroplatinum (CDDP) and TAC-101 (8 mg/kg, p.o., daily) enhanced the anti-tumor effect of CDDP (7 mg/kg, i.v., bolus) against both the growth of implanted tumor and lymphatic metastasis. In addition, this combined treatment significantly prolonged the survival time of LLC tumor-bearing mice as compared to treatment with each agent alone. The anti-activating protein-1 (AP-1) activity of TAC-101 caused inhibition of LLC cell invasion through the repression of expression of urokinase-type plasminogen activator and its receptor. The anti-invasive activity of TAC-101 may be involved in its in vivo anti-metastatic activity. These findings suggest that TAC-101 is a novel anti-cancer agent that may improve the therapeutic modalities for lung cancer patients with metastatic disease.

• Authors: K Murakami, T Yamaura, K Suda, S Ohie, J Shibata, T Toko, Y Yamada, I Saiki
• Journal: Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 90 Issue 11 Pg. 1254-61 (Nov 1999) ISSN: 0910-5050 [Print] Japan
• PMID: 10622538 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents
• Benzoates
• TAC 101
• Transcription Factor AP-1
• Trimethylsilyl Compounds
• Urokinase-Type Plasminogen Activator
• Cisplatin

Topics

• Angiogenesis Inhibitors (pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Benzoates (pharmacology)
• Carcinoma, Lewis Lung (drug therapy, metabolism, secondary)
• Cisplatin (pharmacology)
• Drug Screening Assays, Antitumor
• Female
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Lymphatic Metastasis (prevention & control)
• Mediastinum
• Mice
• Mice, Inbred C57BL
• Neoplasm Invasiveness
• Neoplasm Transplantation
• Reverse Transcriptase Polymerase Chain Reaction
• Transcription Factor AP-1 (metabolism)
• Trimethylsilyl Compounds (pharmacology)
• Urokinase-Type Plasminogen Activator (metabolism)