Stattic suppresses p-STAT3 and induces cell death in T-cell acute lymphoblastic leukemia

The present study investigated the therapeutic potential of Stattic, a selective inhibitor of STAT3, in treating T-cell acute lymphoblastic leukemia (T-ALL). The effects of Stattic on cell viability, STAT3 phosphorylation, apoptosis and autophagy in T-ALL cell lines, and on tumor growth in a xenograft mouse model of T-ALL, were assessed. Methods, including the Cell Counting Kit-8 assay for cell viability, propidium iodide/Annexin V staining for apoptosis detection, western blotting for protein expression analysis, and a xeno- graft mouse model for evaluating in vivo tumor growth, were employed. The results showed that Stattic effectively reduced cell viability in a dose-dependent manner, with significant reductions observed at concentrations of 1.25 µM and above in CCRF-CEM cells (IC₅₀=3.188 µM) and at 2.5 µM and above in Jurkat cells (IC₅₀=4.89 µM) after 24 h of treatment. Concurrently, Stattic significantly suppressed the expression of phosphorylated STAT3, indicating its mechanism of action as a STAT3 pathway inhibitor. Furthermore, Stattic treatment induced both apoptosis and autophagy in CCRF-CEM and Jurkat cells, as evidenced by the respective upregulation of cleaved caspase-3 and LC3B. In a xenograft mouse model of T-ALL, Stattic markedly inhibited tumor growth, with the greatest effect occurring at the highest dose of 30 mg/kg. These results suggested that Stattic holds promise as a thera- peutic agent in T-ALL by modulating key pathways involved in cell survival and proliferation. In conclusion, Stattic exhibited a significant therapeutic potential for T-ALL via a dose-dependent reduction of cell viability, inhibiting STAT3 phosphorylation, and promoting both apoptotic and autophagic cell death; however, further studies are required before clinical application.