title: HepG2 cells recovered from apoptosis show altered drug responses and invasiveness.
abstract: BACKGROUND
  Cancer relapse, associated with increased drug resistance and rate of metastasis, often follows completion of chemotherapy but the cancer escape mechanisms are still incompletely understood. Percutaneous ethanol injection (PEI) has been used for treating hepatocellular carcinoma (HCC) for decades, while the recurrence after PEI treatment remains a major limitation. Recent evidence mounted that cancer cells could survive from chemical induced apoptosis, suggesting a potential route through which cancer relapse may occur. This study focuses on the consequence of HepG2 recovery from ethanol-induced apoptotic event.
  
  
  METHODS
  The model of HepG2 recovery from ethanol-induced apoptotic event was established by live cell imaging, BrdU assay and Western blotting. MTT assay, wound healing assay and invasion assay were used to investigate the behavior of HepG2 after recovery.
  
  
  RESULTS
  HepG2 cells could recover from ethanol-induced apoptosis. These cells changed their behaviors such as drug resistance, mobility and invasiveness. On average, the recovered HepG2 cell clones were found to be 46% more resistant to ethanol and 84% higher in mobility. The recovered clones became 58.2% more sensitive to 5-fluorouracil.
  
  
  CONCLUSIONS
  HepG2 cells can recover from ethanol-induced apoptotic event. These cells became more resistant to ethanol and more invasive. Although the recovered cell clones were more resistant to ethanol, they became more sensitive to 5-fluorouracil treatment.
authors.affiliation: School of Life Sciences, the Chinese University of Hong Kong, Hong Kong, China. mingchiufung@cuhk.edu.hk.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
authors.forename: Chung Sing Timothy
authors.initials: CS
authors.lastname: Wong
authors.forename: Ying
authors.initials: Y
authors.lastname: Choi
authors.forename: Ming Chiu
authors.initials: MC
authors.lastname: Fung
mesh_terms: D055011:Ablation Techniques / Q000379:methods*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D000431:Ethanol / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D000431:Ethanol; D005472:Fluorouracil