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Updated: Jul 18, 2025

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Suppression of Autophagy Can Augment PIK3 Inhibitor Induced Apoptosis in T Lymphoblastic Leukemia Cell Lines
Yu Qing Dong1, Ni Sun1, Xiang Chou Yang1
1Department of Haematology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Objective:
The present study aimed to investigate the effects of the PI3K inhibitor PX-866 or PI-103 combined with the autophagy inhibitor 3-methyladenine (3-MA) on the apoptosis of T lymphoblastic leukemia cells.
Methods:
The proliferation and apoptosis of T lymphoblastic leukemia cell lines were detected by CCK-8 and flow cytometer. The expression of proteins was measured by western blot. The effect of PI3K inhibitors combined with 3-MA on the number of autophagosomes was detected by transmission electron microscopy (TEM).
Results:
We found PX-866 and PI-103 treatment reduced cell viability while increasing apoptosis in CCRF-CEM and Jurkat cells, which was further enhanced when combined with 3-MA. The phosphorylation levels of AKT and mTOR were suppressed by PX-866 or PI-103, which were reversed by 3-MA. Further, the expression of LC3, ATG5, ATG12 and Beclin-1 was upregulated by PX-866 or PI-103 and downregulated by 3-MA. TEM results revealed that the number of autophagosome was increased by PX-866 or PI-103 treatment, which was reversed by 3-MA.
Conclusions:
The results demonstrated that 3-MA could suppress PI3K inhibitor-mediated activation of autophagy to promote the apoptosis of tumor cells. This discovery provided experimental support for constituting a promising strategy for T-cell acute lymphoblastic leukemia (T-ALL) therapy.
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