Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

The Effects of Imatinib Mesylate on Cellular Viability, Platelet Derived Growth Factor and Stem Cell Factor in Mouse Testicular Normal Leydig Cells

Authors
Fatemeh Kheradmand 1
Seyyed Mohammad Reza Hashemnia 2
Nasim Valizadeh 3
Shiva Roshan-Milani 4
1 Department of Biochemistry, Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran
2 Department of Biochemistry, Urmia University of Medical Sciences, Urmia, Iran
3 Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Physiology, Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran
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. Conclusion: 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.
Keywords
Cellular viability
Growth Factors
Imatinib mesylate
Leydig cell
Platelet derived growth factor
Stem cell factor
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Journal of Reproduction & Infertility
Volume 17, Issue 2
Spring 2016
Pages 82-87