Effect of PI3K/mTOR Signal Pathway Inhibitor XL765 on Human Leukemic KG-1 Cells / 中国实验血液学杂志
Journal of Experimental Hematology
; (6): 729-734, 2019.
Artigo
em Chinês
| WPRIM (Pacífico Ocidental)
| ID: wpr-771893
Biblioteca responsável:
WPRO
ABSTRACT
OBJECTIVE@#To explore the effect and possible mechanism of PI3K/mTOR inhibitor XL765 on KG-1 cells in vitro.@*METHODS@#The effect of XL765 on cell proliferation was detected by CCK-8 assay. The colony formation test (200 cells were plated in a plate for 9 days) was used to detect the effect of XL765 on the colony forming ability of KG-1 cells. The apoptosis was assessed by flow cytometry with Annexin V-FITC/PI double staining. Quantitative real-time polymerase chain reaction (q-PCR) was used to detect the expression of cell apoptosis-related genes BCL-2, BAX and caspase-3, Western blot was performed to detect the expression levels of BCL-2, BAX, Caspase-3, and the phosphorylation change of p-PI3K, p-AKT and p-S6K.@*RESULTS@#XL765 effectively inhibited the proliferation and the colony formation of KG-1 cells (P=0.0002). XL765 (150 nmol/L) induced KG-1 cell apoptosis (31.87±1.376%), very statistically significant different from (3.533±0.4179% ) in the control group (P<0.01). Treatment with 150 nmol/L XL765 could in a significantly increase the expression levels of BAX and active caspase-3, and decreases expression level of the BCL-2 (P<0.01). In accordance with these results, the Western blot further confirmed the expression decrease of BCL-2 protein along with the increase BAX and cleaved caspase-3 activity. XL765 statistically significantly down-regulated the phosphorylation levels of PI3K, AKT and S6K.@*CONCLUSION@#PI3K/mTOR inhibitor XL765 substantially suppresses KG-1 cell proliferation and induces apoptosis by inhibiting the activation of PI3K-AKT-mTOR signaling pathway, and regulating the apoptosis-related proteins.
Texto completo:
Disponível
Contexto em Saúde:
ODS3 - Meta 3.4 Reduzir as mortes prematuras devido doenças não transmissíveis
Problema de saúde:
Leucemia
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Quinoxalinas
/
Sulfonamidas
/
Transdução de Sinais
/
Apoptose
/
Fosfatidilinositol 3-Quinases
/
Linhagem Celular Tumoral
/
Proteínas Proto-Oncogênicas c-akt
/
Serina-Treonina Quinases TOR
Limite:
Humanos
Idioma:
Chinês
Revista:
Journal of Experimental Hematology
Ano de publicação:
2019
Tipo de documento:
Artigo