Synergistic antitumor activity of azacitidine and ubenimex on acute myeloid leukemia cells

Acute myeloid leukemia (AML) is a malignancy with high mortality rate and a poor prognosis. Despite advances in targeted agents, effective treatment of AML remains a major clinical challenge. Azacitidine (5AZA) induces apoptosis and has been shown to be therapeutically effective in AML. Ubenimex (Ube), an Aminopeptidase N (APN)/CD13 inhibitor, has demonstrated antitumor activity in solid tumors and hematologic malignancies. This study investigated the antitumor effects of 5AZA combined with Ube in AML using CCK-8, cell apoptosis assay, cell cycle assay, and western blot, as well as in vivo. The results showed that the combination of 5AZA and Ube had a synergistic impact in suppressing the proliferation and inducing apoptosis of AML cell lines compared to the control group. In addition, the expression level of Bax was increased, whereas the expression levels of Bcl-2, p-PI3K and p-AKT were decreased. These effects were found to be reversible by the PI3K specific agonist 740Y-P.