Fostamatinib Inhibits the Proliferation of Ovarian Cancer Cells Through Apoptosis Induction

Background/Aim: Ovarian cancer remains significant challenge due to its high mortality rate and poor prognosis, especially in advanced stages. Despite treatment advancements, issues with resistance and recurrence persist, highlighting the urgent need for new and effective therapies. This study aimed to evaluate fostamatinib, an oral spleen tyrosine kinase inhibitor initially developed for autoimmune diseases, as a potential treatment for ovarian cancer. Materials and Methods: The effects of fostamatinib on ovarian cancer cell lines were assessed using WST-1 assays for cell proliferation. Apoptosis was evaluated through TUNEL assays, DNA fragmentation analysis, and flow cytometry. Western blot analysis was used to detect cleavage of apoptotic proteins, including caspase-3 and PARP, and flow cytometry analyzed cell cycle changes. Results: Fostamatinib treatment resulted in a dose- and time dependent reduction in ovarian cancer cell growth and induced apoptosis, as indicated by increased TUNELpositive cells, DNA fragmentation, and rises in both early and late apoptosis. Western blot analysis showed increased cleavage of apoptotic proteins, including caspase-3 and PARP. Flow cytometry also demonstrated an increase in the sub-G1 phase of the cell cycle, further supporting apoptosis induction. Conclusion: Fostamatinib, by inhibiting cell proliferation and inducing apoptosis, shows promise as repurposed therapeutic agent for ovarian cancer, potentially offering a new approach to improve patient outcomes.