EC-18, a synthetic monoacetyldiacylglyceride, inhibits hematogenous metastasis of KIGB-5 biliary cancer cell in hamster model.
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.
Kim
Myung-Hwan
MH
Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Chang
Heung Moon
HM
Kim
Tae Won
TW
Lee
Sung Koo
SK
Park
Jung-Sun
JS
Kim
Young-Hoon
YH
Lee
Tae Yoon
TY
Jang
Se Jin
SJ
Suh
Chul-Won
CW
Lee
Tae-Suk
TS
Kim
Sang-Hee B
SH
Lee
Sung-Gyu
SG
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D004075:Diglycerides; D005260:Female; D005989:Glycerides / Q000627:therapeutic use*; D008168:Lung / Q000473:pathology; D009362:Neoplasm Metastasis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
C488567:1-palmitoyl-2-linoleoyl-3-acetyl-rac glycerol; D000970:Antineoplastic Agents; D016207:Cytokines; D004075:Diglycerides; D005989:Glycerides; D051197:Toll-Like Receptor 4