The effects of imatinib mesylate on cellular viability, platelet derived growth factor and stem cell factor in mouse testicular normal leydig cells

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