FTY720: a promising agent for treatment of metastatic hepatocellular carcinoma

Clin Cancer Res. 2005 Dec 1;11(23):8458-66. doi: 10.1158/1078-0432.CCR-05-0447.


Purpose: Recurrence after resection and metastasis are common in hepatocellular carcinoma and are associated with poor prognosis. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that FTY720 has an antimetastatic effect on hepatocellular carcinoma cell line through down-regulation of Rac signaling pathway. This study aims to investigate the in vivo antimetastatic potential of FTY720 in an orthotopic nude mice model using metastatic human hepatocellular carcinoma cell lines MHCC-97L (lower metastatic potential) and MHCC-97H (higher metastatic potential).

Experimental design: The nude mice bearing liver tumors were randomized into a treatment group and a control group, each with 12 mice. FTY720 was administered at a dosage of 5 or 10 mg/kg via i.p. injection after 7 days of tumor inoculation. Thirty-five days later, the mice were sacrificed for record of intrahepatic and pulmonary metastases.

Results: After 35 days of FTY720 treatment at the dosages of 5 and 10 mg/kg, all 12 mice in the treatment group were alive and well. FTY720 at the dosages of 5 and 10 mg/kg significantly suppressed the tumor volume and intrahepatic and pulmonary metastases in the metastatic nude mice model. FTY720 suppressed intrahepatic and pulmonary metastases by inhibition of Rac expression, which at least in part down-regulated the vascular endothelial growth factor expression and CD34 staining in a dose-dependent manner.

Conclusion: FTY720 is a promising novel therapeutic drug for treatment of hepatocellular carcinoma metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / secondary
  • Disease Models, Animal
  • Down-Regulation
  • Fingolimod Hydrochloride
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Liver Neoplasms, Experimental / drug therapy*
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / pathology
  • Mice
  • Mice, Nude
  • Microcirculation
  • Neovascularization, Pathologic / prevention & control
  • Propylene Glycols / therapeutic use*
  • Sphingosine / analogs & derivatives
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing
  • rac GTP-Binding Proteins / chemistry
  • rac GTP-Binding Proteins / metabolism


  • Antigens, CD34
  • Immunosuppressive Agents
  • Propylene Glycols
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • rac GTP-Binding Proteins
  • Fingolimod Hydrochloride
  • Sphingosine