title: Evaluation of Effects of Metformin in Primary Ovarian Cancer Cells.
abstract: BACKGROUND
  Ovarian cancer is the third most common cause of cancer in Indian women. Despite an initial 70-80% response rate, most patients relapse within 1-2 years and develop chemoresistance. Hence, identification or repositioning of drugs to resensitise ovarian cancer cells to existing chemotherapy is needed. Traditionally immortalized cell lines have been used in research, but these may contain genetic aberrations and chromosomal abnormalities serving as poor indicators of normal cell phenotype and progression of early-stage disease. The use of primary cells, maintained for only short periods of time in vitro, may serve as the best representative for studying in vivo conditions of the tissues from which they are derived. In this study we have attempted to evaluate the effect of metformin (an antidiabetic drug) in primary ovarian cancer cells because of its promising effect in other solid tumours.
  
  
  METHODS
  Primary cultures of epithelial ovarian cancer cells established from ascitic fluid of untreated ovarian cancer patients were used. The cells were treated with metformin at doses standardized by MTT assay and its ability to induce apoptosis was studied. The cells were analysed for apoptosis and apoptosis related proteins by flow cytometry and western blotting respectively.
  
  
  RESULTS
  Metformin induced apoptosis in ovarian cancer cells, provoking cell cycle arrest in the G0/G1 and S phase. It induced apoptosis in ovarian cancer cells by, down-regulating Bcl-2 and up-regulating Bax expression.
  
  
  CONCLUSIONS
  Metformin was able to induce apoptosis in primary ovarian cancer cells by modulating the expression of Bcl-2 family proteins. These data are relevant to ongoing translational research efforts exploring the chemotherapeutic potential of metformin.
authors.affiliation: Department of Biochemistry, AIIMS, New Delhi, India E-mail : singh_neeta26@rediffmail.com, singh_neeta@hotmail.com.
authors.forename: Seema
authors.initials: S
authors.lastname: Patel
authors.forename: Neeta
authors.initials: N
authors.lastname: Singh
authors.forename: Lalit
authors.initials: L
authors.lastname: Kumar
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008687:Metformin / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D061251:Primary Cell Culture; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D007004:Hypoglycemic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D008687:Metformin