title: Bcl-xL is expressed in ovarian carcinoma and modulates chemotherapy-induced apoptosis.
abstract: OBJECTIVE
  To investigate the role of Bcl-xL in resistance to chemotherapy-induced apoptosis in ovarian carcinoma.
  
  
  METHODS
  Two human ovarian carcinoma cell lines were used in this study: A2780 and SKOV3. A2780 cells were transfected with human Bcl-xL or control plasmid alone. Expression of Bcl-xL in single cell clones was analyzed by flow cytometry and protein expression was confirmed by Western blot. For in vitro chemotherapy-induced death assays, cisplatin and Taxol were used. The percentage of apoptotic cells was determined by nuclear propidium iodide staining followed by flow cytometric analysis. Human ascites samples were used to make tumor lysates which were then analyzed for expression of Bcl-xL protein by Western blot.
  
  
  RESULTS
  A2780 cells express low levels of endogenous Bcl-xL while SKOV3 cells express high amounts as determined by Western blot. In addition, A2780 cells are sensitive to chemotherapy-induced cell death while SKOV3 cells are resistant. To determine if chemoresistance is mediated by expression of Bcl-xL, A2780 cells were transfected with Bcl-xL or control plasmid. Cells were incubated with either cisplatin or Taxol to induce apoptosis. Bcl-xL-expressing cells were highly resistant to cisplatin and Taxol compared with controls (P < 0.05). All samples of malignant ascites analyzed expressed high levels of Bcl-xL on Western blot.
  
  
  CONCLUSIONS
  The results of these studies indicate that Bcl-xL is expressed in ovarian carcinoma, and in A2780 cells functions in a manner analogous to Bcl-2 by inhibiting chemotherapy-induced apoptosis. This may have prognostic significance; previous studies have demonstrated that patients with breast cancer that overexpress Bcl-2 have low-grade, hormonally responsive tumors. In ovarian carcinoma, another Bcl-2 family member, Bcl-xL may be responsible for modulating resistance to chemotherapy-induced apoptosis.
authors.affiliation: Division of Gynecologic Oncology, University of Michigan, Ann Arbor, Michigan, 48109, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Liu
authors.forename: B
authors.initials: B
authors.lastname: Fletcher
authors.forename: C
authors.initials: C
authors.lastname: Page
authors.forename: C
authors.initials: C
authors.lastname: Hu
authors.forename: G
authors.initials: G
authors.lastname: Nunez
authors.forename: V
authors.initials: V
authors.lastname: Baker
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
chemical_list: D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D017239:Paclitaxel; D002945:Cisplatin