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The Effects of Imatinib Mesylate on Cellular Viability, Platelet Derived Growth Factor and Stem Cell Factor in Mouse
Fatemeh Kheradmand1, Seyyed Mohammad Reza Hashemnia2, Nasim Valizadeh3
1Department of Biochemistry, Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran.
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.
Insights
Imatinib treatment reduces mouse leydig cell viability and may impact fertility potential, associated with increased platelet-derived growth factor (PDGF) levels.
Area of Science:
- Reproductive biology
- Cancer therapeutics
- Cellular signaling
Background:
- Growth factors are crucial for normal testicular leydig cell development.
- Anti-cancer drugs like imatinib may disrupt leydig cell function and fertility.
- Imatinib's impact on growth factor production and signaling pathways warrants investigation.
Purpose of the Study:
- To assess cellular viability and growth factor levels (PDGF and SCF) in mouse leydig cells exposed to imatinib.
- To investigate the effect of imatinib on the fertility potential of leydig cells.
Main Methods:
- Mouse TM3 leydig cells were treated with varying imatinib concentrations (0-20 μM) for 2, 4, and 6 days.
- Cellular viability was measured using the MTT assay.
- Growth factor levels were quantified via ELISA; statistical analysis employed ANOVA and Kruskal-Wallis tests.
Main Results:
- Increasing imatinib concentration significantly decreased cellular viability (p<0.05).
- Platelet-derived growth factor (PDGF) levels increased significantly with imatinib exposure (p<0.05).
- Stem cell factor (SCF) levels and treatment duration showed no significant impact on viability or growth factors.
Conclusions:
- Imatinib may impair fertility potential at higher concentrations by reducing leydig cell viability.
- The observed effects of imatinib on leydig cells are linked to PDGF stimulation.
- Further research is needed to explore the long-term consequences of imatinib treatment.
