title: Blocking Bcl-2 leads to autophagy activation and cell death of the HEPG2 liver cancer cell line.
abstract: BACKGROUND
  Apoptosis may be induced after Bcl-2 expression is inhibited in proliferative cancer cells. This study focused on the effect of autophagy activation by ABT737 on anti-tumor effects of epirubicin.
  
  
  METHODS
  Cytotoxic effects of ABT737 on the HepG2 liver cancer cell line were assessed by MTT assay and cell apoptosis through flow cytometry. Mitochondrial membrane potential was measured by fluorescence microscopy. Monodansylcadaverin (MDC) staining was used to detect activation of autophagy. Expression of p53, p62, LC3, and Beclin1, apoptotic or autophagy related proteins, was detected by Western blotting.
  
  
  RESULTS
  ABT737 and epirubicin induced growth inhibition in HepG2 cells in a dose- and time-dependent manner. Both ABT737 and epirubicin alone could induce cell apoptosis with a reduction in mitochondrial membrane potential as well as increased apoptotic protein expression. Further increase of apoptosis was detected when HepG2 cells were co- treated with ABT373 and epirubicin. Furthermore, our results demonstrated that ABT373 or epirubicin ccould activate cell autophagy with elevated autophagosome formation, increased expression of autophagy related proteins and LC3 fluorescent puncta.
  
  
  CONCLUSIONS
  ABT737 influences cancer cells through both apoptotic and autophagic mechanisms, and ABT737 may enhance the effects of epirubicin on HepG2 cells by activating autophagy and inducing apoptosis.
authors.affiliation: Department of General Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China E-mail : dpdoccn@126.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Du
authors.forename: Hua
authors.initials: H
authors.lastname: Cao
authors.forename: Hao-Rong
authors.initials: HR
authors.lastname: Wu
authors.forename: Bao-Song
authors.initials: BS
authors.lastname: Zhu
authors.forename: Hao-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Chun-Wei
authors.initials: CW
authors.lastname: Gu
authors.forename: Chun-Gen
authors.initials: CG
authors.lastname: Xing
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence / Q000379:methods; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2