Annals of clinical and laboratory science · 2023
Suppression of Autophagy Can Augment PIK3 Inhibitor Induced Apoptosis in T Lymphoblastic Leukemia Cell Lines.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Dong Yu Qing, Sun Ni, Yang Xiang Chou, He Mu Qing, Huang He, Guo Wen Jian, Lin Xiao Ji
Аннотация
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.
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.