Myelodysplastic syndromes (MDS) are clonal malignancies of multipotent hematopoietic stem cells, characterized by ineffective hematopoiesis leading to cytopenia. Hypomethylating agents, including azacitidine, have been used for treating MDS with some success; however, the overall survival rate remains poor and, therefore, finding new therapies is necessary. Selinexor, which exerts anticancer effects against some hematologic tumors, is a nuclear export protein inhibitor that blocks cell proliferation and induces apoptosis in various cancer cell lines. We investigated the effects of combined selinexor and azacitidine administration on two MDS cell lines, namely SKM-1 and MUTZ-1. Cells were subjected to a proliferation assay, and the effects of each drug alone, and in combination, were compared. Changes in apoptosis and the cell cycle between groups were also analyzed. Western blotting was conducted to identify the underlying mechanism of action of combined selinexor and azacitidine therapy. The results revealed that the combination of selinexor and azacitidine synergistically inhibited MDS cell proliferation and arrested the cell cycle at the G2/M phase. This combination also promoted MDS cell apoptosis and enhanced p53 accumulation in the nucleus, thereby allowing p53 to be activated and to function as a tumor suppressor. Overall, our results indicate that the combination of selinexor and azacitidine may be a promising approach for treating MDS.
Keywords: Apoptosis; Azacitidine; Myelodysplastic syndromes; P53; Selinexor.
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.