Decitabine inhibits the proliferation of human T‑cell acute lymphoblastic leukemia molt4 cells and promotes apoptosis partly by regulating the PI3K/AKT/mTOR pathway

Zhang,Gang; Gao,Xiaohui; Zhao,Xiaoyan; Wu,Haibing; Yan,Minchao; Li,Yuan; Zeng,Hui; Ji,Zhaoning; Guo,Xiaojun

doi:10.3892/ol.2021.12601

Decitabine inhibits the proliferation of human T‑cell acute lymphoblastic leukemia molt4 cells and promotes apoptosis partly by regulating the PI3K/AKT/mTOR pathway

Authors:
- Gang Zhang
- Xiaohui Gao
- Xiaoyan Zhao
- Haibing Wu
- Minchao Yan
- Yuan Li
- Hui Zeng
- Zhaoning Ji
- Xiaojun Guo
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Affiliations: Department of Hematology, First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China, Department of Pediatrics, First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China, Department of Medical Oncology, The Cancer Center, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China
Published online on: March 2, 2021 https://doi.org/10.3892/ol.2021.12601
Article Number: 340
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

T cell acute lymphoblastic leukemia (T‑ALL) is a highly aggressive hematological cancer; however, there is a lack of effective chemotherapeutic or targeted drugs for the treatment of T‑ALL. Decitabine is a DNA demethylation agent but it has not been used for T‑ALL treatment. Therefore, the present study aimed to assess the inhibitory effect of decitabine on T‑ALL molt4 cells and determine its regulatory role in the PI3K/AKT/mTOR pathway. Molt4 cells were stimulated with decitabine in vitro, after which cell proliferation, apoptosis and cell cycle analyses were performed to assess cell viability. Subcellular morphology was observed using transmission electron microscopy. Expression levels of phosphate and tension homology (PTEN), genes involved in the PI3K/AKT/mTOR pathway and the corresponding downstream genes were analyzed using reverse transcription‑quantitative PCR and western blotting. The results showed that decitabine induced apoptosis, inhibited proliferation and arrested molt4 cells in the G2 phase. Following decitabine intervention, an increase in the number of lipid droplets, autophagosomes and mitochondrial damage was observed. At concentrations of 1 and 10 µM, decitabine downregulated the expression of PI3K, AKT, mTOR, P70S6 and eukaryotic initiating factor 4E‑binding protein 1, which in turn upregulated PTEN expression; however, 50 µM decitabine downregulated PTEN levels. Overall, these results demonstrated that decitabine reduced the viability of molt4 cells partly by inhibiting the PI3K/AKT/mTOR pathway via PTEN, especially at low decitabine concentrations.

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