EC-18, a Synthetic Monoacetyldiacylglyceride, Inhibits Hematogenous Metastasis of KIGB-5 Biliary Cancer Cell in Hamster Model.
10.3346/jkms.2009.24.3.474
- Author:
Myung Hwan KIM
1
;
Heung Moon CHANG
;
Tae Won KIM
;
Sung Koo LEE
;
Jung Sun PARK
;
Young Hoon KIM
;
Tae Yoon LEE
;
Se Jin JANG
;
Chul Won SUH
;
Tae Suk LEE
;
Sang Hee KIM
;
Sung Gyu LEE
Author Information
1. Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
EC-18;
Anti-Tumor Effect;
TLR-4;
Biliary Cancer
- MeSH:
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
- From:Journal of Korean Medical Science
2009;24(3):474-480
- CountryRepublic of Korea
- Language:English
-
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.
