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

Kevin T. Ng, Kwan Man, Joanna W. Ho, Chris K. Sun, Kin Wah Lee, Yi Zhao, Chung Mau Lo, Ronnie T. Poon, Sheung Tat Fan

Research output: Journal article publicationJournal articleAcademic researchpeer-review

26 Citations (Scopus)

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-Aktser473and 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.
Original languageEnglish
Pages (from-to)375-380
Number of pages6
JournalInternational Journal of Oncology
Volume30
Issue number2
Publication statusPublished - 1 Feb 2007
Externally publishedYes

Keywords

  • AKT signaling pathway
  • Apoptosis
  • Focal adhesion kinase
  • FTY720
  • Hepatocellular carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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