Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2005; 11(48): 7602-7606
Published online Dec 28, 2005. doi: 10.3748/wjg.v11.i48.7602
Cyclosporine A, FK-506, 40-0-[2-hydroxyethyl]rapamycin and mycophenolate mofetil inhibit proliferation of human intrahepatic biliary epithelial cells in vitro
Chao Liu, Thomas Schreiter, Andrea Frilling, Uta Dahmen, Christoph E Broelsch, Guido Gerken, Ulrich Treichel
Chao Liu, Thomas Schreiter, Guido Gerken, Ulrich Treichel, Department of Gastroenterology and Hepatology, University Hospital Essen, Germany
Andrea Frilling, Uta Dahmen, Christoph E Broelsch, Department of General Surgery and Transplantation, University Hospital Essen, Germany
Chao Liu, Department of General Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 West Yan Jiang Road, 510120 Guangzhou, Guangdong Province, China. mdliuchao@hotmail.com,
Author contributions: All authors contributed equally to the work.
Correspondence to: Ulrich Treichel, MD, Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany. ulrich.treichel@uni-essen.de
Telephone: +49-201-723-3612 Fax: +49-201-723-5970
Received: December 30, 2004
Revised: February 13, 2005
Accepted: February 18, 2005
Published online: December 28, 2005
Abstract

AIM: To investigate the effect of cyclosporine A (CsA), FK-506, and mycophenolate mofetil (MMF) and 40-0-[2-hydroxyethyl]rapamycin (RAD) on proliferation of human intrahepatic biliary epithelial cells (BECs) in vitro.

METHODS: BECs were isolated from six human liver tissuespecimens with the immunomagnetic separation method and treated with different concentrations of CsA, FK-506, RAD, and MMF in vitro. Proliferation of the cells was measured by MTT assay at 24 and 48 h after treatment, respectively. One-way analysis of variance was used to analyze the results. Expression of CK 19 in BECs was monitored by flow cytometry and Western blot.

RESULTS: Six lines of BECs were established. They survived for 4-18 wk in vitro. Flow cytometry analysis showed that these cells always expressed CK19. CsA, FK-506, RAD, and MMF inhibited proliferation of BECs in a dose-dependent manner. The lowest concentration of CsA, FK-506, RAD, and MMF to inhibit proliferation of BECs (P<0.05) was 500, 100, 0.25, and 100 µg/L, respectively. However, the expression of CK19 by BECs was not changed.

CONCLUSION: CsA, FK-506, RAD, and MMF have an antiproliferative effect on human intrahepatic BECs in vitro, while RAD has the strongest growth-inhibitory effect. Their possible effects on liver regeneration and bile duct injury in transplant patients should be further investigated.

Keywords: Cyclosporine A; FK-506, Rapamycin; Mycophenolate mofetil; Biliary epithelial cells