title: Epithelial cell adhesion molecule in human hepatocellular carcinoma cell lines: a target of chemoresistence.
abstract: BACKGROUND
  The low survival rate of hepatocellular carcinoma (HCC) is partly attributable to its resistance to existing chemotherapeutic agents. Until now, there have been limited chemotherapeutic agents for liver cancer. Epithelial cell adhesion molecule (EpCAM) has been found to be over-expressed during stages of carcinogenesis and has been associated with poor overall survival in many cancers. The aim of this study was to evaluate EpCAM expression in HCC and evaluate the effects of EpCAM to established chemotherapy.
  
  
  METHODS
  Three human hepatocellular carcinoma cell lines--HepG2, Hep3B and HuH-7--were pre- and post-treated with doxorubicin, 5-fluorouracil (5-FU) and cisplatin. Cell viability and EpCAM protein expression were measured by MTT assay and Western Blotting respectively. EpCAM positive cells were analyzed by flow cytometry. To evaluate the effects of doxorubicin efficacy on EpCAM positive cells, a small interfering RNA (siRNA) specific to EpCAM was transfected into the cells and treated with doxorubicin.
  
  
  RESULTS
  EpCAM was significantly down-regulated by doxorubicin treatment in all three HCC cell lines (P <0.05 or 0.01). EpCAM expression was down-regulated by the 5-FU and cisplatin in HepG2 cells, however the EpCAM expression was up-regulated by 5-FU and cisplatin in Hep3B cell line. EpCAM expression was down-regulated by 5-FU, and up-regulated by cisplatin in Huh-7 cell line. Flow cytometry assay showed doxorubicin exposure decreased EpCAM positive cell quantities in three HCC cell lines. EpCAM siRNA knock-down attenuated cell mortality after doxorubicin exposure.
  
  
  CONCLUSIONS
  All of these findings demonstrate that EpCAM is one of targets of chemoresistence.
authors.affiliation: Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
authors.forename: Russell W
authors.initials: RW
authors.lastname: Farmer
authors.affiliation: School of Life Science, Southwest University, Chongqing, 400716, China.
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, 40202, USA. robert.martin@louisville.edu.|Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, 315 E. Broadway - #312, Louisville, KY, 40202, USA. robert.martin@louisville.edu.
authors.forename: Robert C G
authors.initials: RC
authors.lastname: Martin
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D000071858:Epithelial Cell Adhesion Molecule / Q000096:biosynthesis* / Q000235:genetics; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D034741:RNA, Small Interfering
chemical_list: C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D034741:RNA, Small Interfering; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil
keywords: 5-FU; Cisplatin; Doxorubicin; Epithelial cell adhesion molecule; Hepatocellular carcinoma