title: The Effects of Imatinib Mesylate on Cellular Viability, Platelet Derived Growth Factor and Stem Cell Factor in Mouse Testicular Normal Leydig Cells.
abstract: BACKGROUND
  Growth factors play an essential role in the development of tumor and normal cells like testicular leydig cells. Treatment of cancer with anti-cancer agents like imatinib mesylate may interfere with normal leydig cell activity, growth and fertility through failure in growth factors' production or their signaling pathways. The purpose of the study was to determine cellular viability and the levels of, platelet derived growth factor (PDGF) and stem cell factor (SCF) in normal mouse leydig cells exposed to imatinib, and addressing the effect of imatinib on fertility potential.
  
  
  METHODS
  The mouse TM3 leydig cells were treated with 0 (control), 2.5, 5, 10 and 20 μM imatinib for 2, 4 and 6 days. Each experiment was repeated three times (15 experiments in each day).The cellular viability and growth factors levels were assessed by MTT and ELISA methods, respectively. For statistical analysis, one-way ANOVA with Tukey's post hoc and Kruskal-Wallis test were performed. A p-value less than 0.05 was considered statistically significant.
  
  
  RESULTS
  With increasing drug concentration, cellular viability decreased significantly (p<0.05) and in contrast, PDGF levels increased (p<0.05). Different imatinib concentrations had no significant effect on SCF level. Increasing the duration of treatment from 2 to 6 days had no obvious effect on cellular viability, PDGF and SCF levels.
  
  
  CONCLUSIONS
  Imatinib may reduce fertility potential especially at higher concentrations in patients treated with this drug by decreasing cellular viability. The effect of imatinib on leydig cells is associated with PDGF stimulation. Of course future studies can be helpful in exploring the long term effects of this drug.
authors.affiliation: Department of Biochemistry, Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Kheradmand
authors.affiliation: Department of Biochemistry, Urmia University of Medical Sciences, Urmia, Iran.
authors.forename: Seyyed Mohammad Reza
authors.initials: SM
authors.lastname: Hashemnia
authors.affiliation: Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nasim
authors.initials: N
authors.lastname: Valizadeh
authors.affiliation: Department of Physiology, Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran.
authors.forename: Shiva
authors.initials: S
authors.lastname: Roshan-Milani
keywords: Cellular viability; Growth factors; Imatinib mesylate; Leydig cells; Platelet derived growth factor; Stem cell factor