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

Li,Chia-Ling; Chen,Han-Yu; Yen,Jiin-Cherng; Yu,Sheng-Jie; Chou,Ting-Yu; Yeh,Sih-Wen; Chuang,Huai-Yu; Huang,Fang-Liang

doi:10.3892/mmr.2024.13416

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

Authors:
- Chia-Ling Li
- Han-Yu Chen
- Jiin-Cherng Yen
- Sheng-Jie Yu
- Ting-Yu Chou
- Sih-Wen Yeh
- Huai-Yu Chuang
- Fang-Liang Huang
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Affiliations: Children's Medical Center, Taichung Veterans General Hospital, Taichung 407, Taiwan, R.O.C., Department of Physical Therapy, Hung‑Kuang University, Taichung 433, Taiwan, R.O.C., Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei 112, Taiwan, R.O.C., Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan, R.O.C., Department of Pathology, Tri‑Service General Hospital Penghu Branch, Magong, Penghu County 880, Taiwan, R.O.C.
Published online on: December 10, 2024 https://doi.org/10.3892/mmr.2024.13416
Article Number: 51
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 xenograft 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 therapeutic 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.

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