Suppression of Autophagy Can Augment PIK3 Inhibitor Induced Apoptosis in T Lymphoblastic Leukemia Cell Lines.
Ann Clin Lab Sci
; 53(4): 598-606, 2023 Jul.
Article
in En
| MEDLINE
| ID: mdl-37625845
ABSTRACT
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.Key words
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphoma, Non-Hodgkin
/
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Limits:
Humans
Language:
En
Journal:
Ann Clin Lab Sci
Year:
2023
Document type:
Article
Affiliation country:
China
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA