The Journal of Medical Investigation
Online ISSN : 1349-6867
Print ISSN : 1343-1420
ISSN-L : 1343-1420
Originals
Inhibitory effect of FK506 and Cyclosporine A on the growth and invasion of human liver cancer cells
Manabu SakaiHidenori MiyakeSeiki TashiroYuushi OkumuraHiroshi Kido
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2004 Volume 51 Issue 1,2 Pages 63-69

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Abstract

Background: The prognosis of liver transplantation for liver cancer is determined by recurrence in the liver graft. In this study, the effects of immunosuppressors, FK506 and cyclosporine A (CsA) on the migration of liver cancer cells were investigated.
Methods: The effects of FK506 at concentrations of 1-100 ng/mL and CsA at 1-1000 ng/mL on the growth of poorly and well differentiated human hepatocellular carcinoma cell lines, HLE and HuH-7, respectively, were examined. After treatment of these cells with FK506 and CsA, the growth of these cells, their cytotoxicities and invasion assay on the Matrigel basement membrane invasion chamber were evaluated. In addition, the effects of FK506 and CsA on the changes in the production of a soluble intercellular adhesion molecule-1 (sICAM-1) of these cells were measured.
Results: FK506 and CsA at concentrations of 1-10 ng/mL inhibited the growth of both HLE and HuH-7 and those immunosuppressors at concentrations over 100 ng/mL exhibited cytotoxicity on these cells. FK506 at concentration of 1ng/mL significantly inhibited the invasion of poorly differentiated HLE, but not well differentiated HuH-7, after treatment for 2-5 days in culture (p<0.05), but FK506 at 10 ng/mL showed less inhibitory efficient. CsA at concentrations of 1-10 ng/mL, however, did not inhibit or transiently inhibited the invasion of both cell lines. The production of ICAM-1 in HLE and HuH-7 was suppressed by FK506 at concentrations of 1-10 ng/mL after treatment for 3-5 days but the effect was not significant in the initial phase at days 1-2 and the last phase at days 5-6.
Conclusions: FK506, but not CsA, at a clinical dose of 1ng/mL significantly inhibited the invasion of the poorly-differentiated HLE, but not HuH-7 and also inhibited the production of sICAM-1 in HLE.

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© 2004 by The University of Tokushima Faculty of Medicine
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