Effects of selinexor, a nuclear trasport inhibitor, on spematogonium and spermatid cells

In this thesis, the potential cytotoxic and apoptotic effects of SLX, a nuclear transport inhibitor, on wage-derived spermatogonium (GC1) and spermatid (GC2) cell lines were investigated under in vitro conditions. SLX, one of the new generation of targeted agents in cancer therapy, inhibits intracellular protein transport via Exportin-1 (XPO1) protein and induces apoptosis by inducing intracellular accumulation of tumor suppressor proteins. However, information on the effects of this drug on healthy germ cells is very limited. In this study, cell viability was evaluated by MTT, cell proliferation by colony formation assay, cell migration by wound healing model and expression levels of apoptotic and DNA damage response proteins BAX, CAS-3, ATM and BRCA1 were analyzed by immunocytochemistry (ICC) in GC1 and GC2 cell lines. The results show that SLX dose-dependently decreased cell viability and significantly suppressed colony formation and migration capacity in both cell lines. In addition, increases in apoptosis markers such as BAX and CAS-3 and changes in immunoreactivity have been detected in DNA damage response proteins such as ATM and BRCA1. The data suggest that SX has adverse effects on proliferation, migration and viability of germ cells and that these effects are mediated through apoptosis and DNA damage response mechanisms. This study aims to provide a scientific basis for the development of future preventive strategies by revealing the possible risks of SLX for fertility at the cellular level for the first time.