학술논문
Dual PI3K/mTOR inhibitor NVP-BEZ235 decreases the proliferation of doxorubicin-resistant K562 cells
phosphoinositide 3-kinase/mammalian target of rapamycin
phosphoinositide 3-kinase/mammalian target of rapamycin
Document Type
Report
Author
Source
Molecular Medicine Reports. April 2021, Vol. 23 Issue 4
Subject
Language
English
ISSN
1791-2997
Abstract
Introduction Leukemias, presenting with increased numbers of leucocytes, are a group of malignant disorders. Globally, the number of newly diagnosed leukemia patients increased from 3,545,000 in 1990 to 5,185,000 in [...]
Acute myelogenous leukemia (AML) is frequently accompanied by a poor prognosis. The majority of patients with AML will experience recurrence due to multiple drug resistance. Our previous study reported that targeting the mTOR pathway may increase cell sensitivity to doxorubicin (Doxo) and provide an improved therapeutic approach to leukemia. However, the effect and mechanism of action of NVP-BEZ235 (BEZ235), a dual inhibitor of PI3K/mTOR, on Doxo-resistant K562 cells (K562/A) is yet to be elucidated. Therefore, the aim of the present study was to investigate the effects of BEZ235 on K562/A cell proliferation. K562/A cells was investigated using CCK-8, flow cytometry and western blotting, following BEZ235 treatment. It was observed that BEZ235 significantly decreased the viability of K562/A cells. In addition, BEZ235 arrested K562/A cells at the [G.sub.0]/[G.sub.1] phase, and reduced the protein expression levels of CDK4, CDK6 and cyclin D1. Apoptotic cells were more frequently detected in K562/A cells treated with BEZ235 compared with the control group (12.97 [+ or -] 0.91% vs. 7.37 [+ or -] 0.42%, respectively; P Key words: chronic myelogenous leukemia, NVP-BEZ235, doxorubicin-resistant, mTOR, AKT
Acute myelogenous leukemia (AML) is frequently accompanied by a poor prognosis. The majority of patients with AML will experience recurrence due to multiple drug resistance. Our previous study reported that targeting the mTOR pathway may increase cell sensitivity to doxorubicin (Doxo) and provide an improved therapeutic approach to leukemia. However, the effect and mechanism of action of NVP-BEZ235 (BEZ235), a dual inhibitor of PI3K/mTOR, on Doxo-resistant K562 cells (K562/A) is yet to be elucidated. Therefore, the aim of the present study was to investigate the effects of BEZ235 on K562/A cell proliferation. K562/A cells was investigated using CCK-8, flow cytometry and western blotting, following BEZ235 treatment. It was observed that BEZ235 significantly decreased the viability of K562/A cells. In addition, BEZ235 arrested K562/A cells at the [G.sub.0]/[G.sub.1] phase, and reduced the protein expression levels of CDK4, CDK6 and cyclin D1. Apoptotic cells were more frequently detected in K562/A cells treated with BEZ235 compared with the control group (12.97 [+ or -] 0.91% vs. 7.37 [+ or -] 0.42%, respectively; P Key words: chronic myelogenous leukemia, NVP-BEZ235, doxorubicin-resistant, mTOR, AKT