مهار مسیرهای سیگنالی فاکتورهای رشد توسط داروی ایماتینیب مسیلات در سلول‌های لایدیگ نرمال موشی

  Background & Aims : Cancer cells proliferation may be mediated by abnormal phosphorylation of signaling pathways downstream of tyrosine kinase receptors such as Platelet derived growth factor receptor α (PDGFR-α) and β (PDGFR-β). We aimed to study the phosphorylation level of PDGFR-α and PDGFR-β and apoptosis in mouse normal leydig cells being exposed to Imatinib.   Materials & Methods : The mouse TM3 leydig cells were treated with 0, 2.5,5,10 and 20 μM Imatinib for 2, 4, and 6 days. The apoptosis and phosphorylation level of PDGFRs were assessed by caspase-3 activities colorimetric and fluorescence immunoassay methods, respectively. For statistical analysis, one-way ANOVA and T-test were performed.   Results : Phosphorylation level of PDGFR-α in the treated (0.21±0.001) and control cells (0.35±0.13) was significantly different (P<0.05), and its level decreased with increasing drug dosage (P<0.05). PDGFR-β level and apoptosis had no significant differences between groups, although PDGFR-β level decreased significantly with increasing exposure duration (P<0.05).   Conclusion : By inhibition of signaling pathways downstream of growth factors specifically PDGFR-α phosphorylation blockage in normal leydig cells, Imatinib may interfere with cellular growth. It seems that this drug has no effect on apoptotic pathways.   SOURCE: URMIA MED J 2013: 24(9): 718 ISSN: 1027-3727