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Marked suppression of tumor growth by FTY720 in a rat liver tumor model: the significance of down-regulation of cell survival Akt pathway.

Abstract
We aim to investigate the anticancer effect of a novel immunomodulator FTY720 on a rat orthotopic liver tumor model. A buffalo rat orthotopic liver tumor model was established by injection of a buffalo hepatoma cell line MH7777 into the right portal vein. FTY720 was administered by intraperitoneal injection starting at 10 days after tumor cell injection at a dosage of 5 mg/kg/day. FTY720 markedly suppressed tumor growth and inhibited tumor progression by selective induction of apoptosis of tumor cells via down-regulation of phospho-Akt(ser473) and up-regulation of cleaved caspase-3, together with decrease of focal adhesion kinase. Moreover, the proliferation index of tumor cells was significantly reduced to 15.92+/-5.03% by FTY720 compared with that of 42.92+/-4.47% in the control group (p<0.001). In addition, we confirmed that FTY720 caused no effect on infiltrated lymphocyte in tumor tissue. We conclude that FTY720 is an effective anticancer agent for liver tumor in a rat model without affecting the immune system of the host.
AuthorsKevin T Ng, Kwan Man, Joanna W Ho, Chris K Sun, Terence K Lee, Yi Zhao, Chung Mau Lo, Ronnie T Poon, Sheung Tat Fan
JournalInternational journal of oncology (Int J Oncol) Vol. 30 Issue 2 Pg. 375-80 (Feb 2007) ISSN: 1019-6439 [Print] Greece
PMID17203219 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Propylene Glycols
  • Proto-Oncogene Proteins c-akt
  • Fingolimod Hydrochloride
  • Sphingosine
Topics
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Disease Progression
  • Down-Regulation
  • Fingolimod Hydrochloride
  • Gene Expression Regulation, Neoplastic
  • Immunosuppressive Agents (pharmacology)
  • Liver Neoplasms (drug therapy, immunology, metabolism)
  • Lymphocytes (metabolism)
  • Neoplasm Transplantation
  • Propylene Glycols (pharmacology)
  • Proto-Oncogene Proteins c-akt (physiology)
  • Rats
  • Sphingosine (analogs & derivatives, pharmacology)
  • Up-Regulation

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