J Korean Med Sci.  2009 Jun;24(3):474-480. 10.3346/jkms.2009.24.3.474.

EC-18, a Synthetic Monoacetyldiacylglyceride, Inhibits Hematogenous Metastasis of KIGB-5 Biliary Cancer Cell in Hamster Model

Affiliations
  • 1Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
  • 2Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
  • 3Asan Institute for Life Sciences, Seoul, Korea.
  • 4R & D Center, EnzyChem Co. Ltd, Daejon, Korea.
  • 5Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. sglee2@amc.seoul.kr
  • 6Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Abstract

EC-18 (monoacetyldiacylglyceride) stimulates T cell production of IL-2, IL-4, IL-12, IFN-gamma, and GM-CSF in vitro. To study the effects of these cytokines stimulated by EC-18 on cancer cells, we applied hamster biliary cancer model, a difficult cancer to treat. Cancer (KIGB-5) cells were given intravenously to produce hematogenous metastatic lung lesions which were treated with EC-18 at 10, 25, and 50 mg/kg/day respectively. The fourth group was untreated control. At 4th, 8th, and 12th week the lungs were examined. EC-18 treated groups showed only a few microscopic lung lesions and no evidence of metastatic lesion with highest dose whereas widespread gross lung lesions were observed in untreated control. To investigate whether the anti-tumor effect of EC-18 is associated with suppression of tumor cell Toll-like receptor 4 (TLR-4) expression in addition to stimulation of the immune cells, KIGB-5 cells were exposed to LPS with or without EC-18. TLR-4 mRNA and protein expression, measured by reverse transcriptase PCR (RT-PCR), real-time quantitative PCR and western blot analysis, showed suppression of TLR-4 expression in KIGB-5 cells treated with EC-18 compared with control. In conclusion, EC-18 has a significant anti-tumor effect in this experimental model of biliary cancer suggesting potential for clinical application to this difficult cancer.

Keyword

EC-18; Anti-Tumor Effect; TLR-4; Biliary Cancer

MeSH Terms

Animals
Antineoplastic Agents/*therapeutic use
Biliary Tract Neoplasms/*drug therapy/pathology
Cricetinae
Cytokines/metabolism
Female
Glycerides/*therapeutic use
Lung/pathology
Neoplasm Metastasis
T-Lymphocytes/immunology/metabolism
Toll-Like Receptor 4/genetics/metabolism
Tumor Cells, Cultured
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