This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ho, J. W.Y. Articles by Fan, S. T. Search for Related Content PubMed PubMed Citation Articles by Ho, J. W.Y. Articles by Fan, S. T.

Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China

Requests for reprints: Ronnie T.P. Poon, Department of Surgery, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China. Phone: 852-28553641; Fax: 852-28175475. E-mail: poontp{at}hkucc.hku.hk

In this study, we aimed to evaluate the potential anticancer and antiangiogenic effects of FTY720 on hepatocellular carcinoma. In vitro, chemosensitivity was tested on hepatoma cells, nontumorigenic, immortalized hepatocyte cells, as well as human umbilical vein endothelial cells (HUVEC). Moreover, effect of FTY720 on cell cycle and apoptosis was analyzed. In addition, a number of angiogenesis-associated assays were carried out. The in vivo effect of the drug on hepatocellular carcinoma tumor growth on nude mice was studied. Tissues obtained were analyzed in terms of proliferation, apoptosis, tumor microvessel density, and tumor vascular permeability. Compared with the MIHA cells, the hepatoma cell lines as well as HUVECs were found to be highly sensitive to the drugs in the aspect that FTY720 could induce G₁ arrest and apoptosis in the hepatoma cells. Furthermore, FTY720 significantly decreased invasion, migration, and capillary tube formation of HUVECs at very low doses. In vivo study showed that tumor growth was significantly suppressed in the FTY720-treated animals, and staining of the tissue sections showed decreased tumor cell proliferation and increased tumor cell apoptosis in the treatment groups. Interestingly, significant reductions in tumor microvessel density and tumor vascular permeability were also found in the FTY720-treated groups. In conclusion, FTY720 not only shows potent antiangiogenic effects but is also cytotoxic toward hepatoma cells. Results from our preclinical study suggest that FTY720 can be selected as a good candidate for the treatment of hepatocellular carcinoma.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 1/17/05; revised 7/ 2/05; accepted 7/15/05.

This article has been cited by other articles:

				C. K. Sun, K. Man, K. T. Ng, J. W. Ho, Z. X. Lim, Q. Cheng, C.-M. Lo, R. T. Poon, and S.-T. Fan Proline-rich tyrosine kinase 2 (Pyk2) promotes proliferation and invasiveness of hepatocellular carcinoma cells through c-Src/ERK activation Carcinogenesis, November 1, 2008; 29(11): 2096 - 2105. [Abstract] [Full Text] [PDF]

				J.-H. Hung, Y.-S. Lu, Y.-C. Wang, Y.-H. Ma, D.-S. Wang, S. K. Kulp, N. Muthusamy, J. C. Byrd, A.-L. Cheng, and C.-S. Chen FTY720 Induces Apoptosis in Hepatocellular Carcinoma Cells through Activation of Protein Kinase C {delta} Signaling Cancer Res., February 15, 2008; 68(4): 1204 - 1212. [Abstract] [Full Text] [PDF]

				A. S. Don, C. Martinez-Lamenca, W. R. Webb, R. L. Proia, E. Roberts, and H. Rosen Essential Requirement for Sphingosine Kinase 2 in a Sphingolipid Apoptosis Pathway Activated by FTY720 Analogues J. Biol. Chem., May 25, 2007; 282(21): 15833 - 15842. [Abstract] [Full Text] [PDF]

				M. Murph, T. Tanaka, S. Liu, and G. B. Mills Of Spiders and Crabs: The Emergence of Lysophospholipids and Their Metabolic Pathways as Targets for Therapy in Cancer. Clin. Cancer Res., November 15, 2006; 12(22): 6598 - 6602. [Abstract] [Full Text] [PDF]