Abstract | BACKGROUND: METHODOLOGY/PRINCIPAL FINDINGS: An orthotopic liver tumor model in Buffalo rat was established using the hepatocellular carcinoma cell line McA-RH7777. Two weeks after orthotopic liver tumor implantation, the rats underwent liver resection for tumor-bearing lobe and partial hepatic I/R injury. FTY720 (2 mg/kg) was administered through the inferior caval vein before and after I/R injury. Blood samples were taken at days 0, 1, 3, 7, 14, 21 and 28 for detection of circulating EPCs (CD133+CD34+). Our results showed that intrahepatic and lung metastases were significantly inhibited together with less tumor angiogenesis by FTY720 treatment. The number of circulating EPCs was also significantly decreased by FTY720 treatment from day 7 to day 28. Hepatic gene expressions of CXCL10, VEGF, CXCR3, CXCR4 induced by hepatic I/R injury were down-regulated in the treatment group. CONCLUSIONS/SIGNIFICANCE:
FTY720 suppressed liver tumor metastasis after liver resection marred by hepatic I/R injury in a rat liver tumor model by attenuating hepatic I/R injury and reducing circulating EPCs.
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Authors | Chang Xian Li, Yan Shao, Kevin T P Ng, Xiao Bing Liu, Chang Chun Ling, Yuen Yuen Ma, Wei Geng, Sheung Tat Fan, Chung Mau Lo, Kwan Man |
Journal | PloS one
(PLoS One)
Vol. 7
Issue 2
Pg. e32380
( 2012)
ISSN: 1932-6203 [Electronic] United States |
PMID | 22384233
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Immunosuppressive Agents
- Propylene Glycols
- Fingolimod Hydrochloride
- Sphingosine
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Topics |
- Animals
- Carcinoma, Hepatocellular
(drug therapy, pathology, surgery)
- Cell Line, Tumor
- Fingolimod Hydrochloride
- Gene Expression Regulation, Neoplastic
- Humans
- Immunosuppressive Agents
(pharmacology)
- Liver
(drug effects, pathology, surgery)
- Liver Neoplasms
(drug therapy, pathology, surgery)
- Neoplasm Metastasis
- Neoplasm Transplantation
- Neovascularization, Pathologic
- Propylene Glycols
- Rats
- Reperfusion Injury
- Sphingosine
(analogs & derivatives, physiology)
- Stem Cells
(cytology)
- Time Factors
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