| Popis: |
Background: The PI3K/Akt signaling pathway plays an important role in the occurrence and development of tumors, and various PI3K inhibitors have been reported in antitumor. However, PI3K inhibitors can induce autophagy and activation of autophagy can promote drug resistance of tumor cells or improve cell survival. Therefore, 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 acute T-acute lymphoblastic leukemia cells lines CCRF-CEM and Jurkat cells. Methods and results: We found PX-866 and PI-103 treatment significantly reduced cell viability whilst also greatly increasing apoptosis in CCRF-CEM and Jurkat cells. The efficacy of this treatment was further enhanced when combined with 3-MA. The phosphorylation levels of AKT and mTOR in CCRF-CEM and Jurkat cells were significantly suppressed by the introduction of PX-866 or PI-103, the effects of which were reversed by co-treatment with 3-MA. In addition, the expression of LC3, ATG5, ATG12 and Beclin-1 were found to be significantly upregulated by PX-866 or PI-103 treatment and were markedly downregulated by the co-administration of 3-MA. TEM results revealed that the number of autophagic vacuoles in CCRF-CEM and Jurkat cells was increased by PX-866 and PI-103 treatment, which was reversed by 3-MA co-treatment. Conclusions: The combination of PI3K and autophagy inhibitors reduced cell viability and induced apoptosis in T-acute lymphoblastic leukemia cells. This discovery provided a new way to improve the effectiveness of anti-tumor strategies in T-cell acute lymphoblastic leukemia. |
