title: Effects of epidermal growth factor receptor inhibitor genistein on proliferative cholangitis in rats.
abstract: BACKGROUND
  Many strategies for treating hepatolithiasis neglect the therapy for associated proliferative cholangitis (PC), which is the root cause of residual and recurrent stones and biliary strictures, resulting in an unsatisfactory therapeutic outcome. Epidermal growth factor receptor (EGFR) expression is a dominant component in cell proliferation. The aim of this study was to investigate the effect of EGFR inhibitor genistein on PC in rats.
  
  
  METHODS
  The rat PC model was established by introducing a nylon thread into the bile duct. Different doses of genistein were administered directly into the bile duct. The effectiveness of genistein on PC was assessed by histology, immunohistochemistry for EGFR, and RT-PCR for EGFR mRNA.
  
  
  RESULTS
  The proliferation of biliary epithelium, and fibrous tissue, and the hyperplasia of peribiliary gland in PC were indeed suppressed by genistein, and this antiproliferative effect presented a significant dose-response relationship. The structure of biliary tissue in the high-dose group (genistein 6.0mg/kg) had approached that of the normal bile duct. Compared with the PC model, the levels of expression of EGFR mRNA and protein in the genistein-treated groups were reduced gradually with the increase of genistein dosage, and the level of expression of EGFR mRNA and protein in the high-dose group had neared that of the normal bile duct.
  
  
  CONCLUSIONS
  Direct administration of genistein into the bile duct suppressed PC in a rat model, and may provide a novel strategy towards improving the prognosis of patients with hepatolithiasis.
authors: Department of Hepatic and Vascular Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu, China.
authors: Li
authors: L
authors: Jiang
authors: Li-Sheng
authors: LS
authors: Jiang
authors: Lu-Nan
authors: LN
authors: Yan
authors: Fu-Yu
authors: FY
authors: Li
authors: Wei
authors: W
authors: Wang
authors: Nan-Sheng
authors: NS
authors: Cheng
authors: Tian-Fu
authors: TF
authors: Wen
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002761:Cholangitis / Q000188:drug therapy* / Q000473:pathology; D004396:Coloring Agents; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008297:Male; D010503:Periodic Acid-Schiff Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004396:Coloring Agents; D012333:RNA, Messenger; D019833:Genistein; D066246:ErbB Receptors