[Effect of endoplasmic reticulum stress induced by all-trans retinoic acid on apoptosis of FLT3-ITD mutated leukemia cells by activating autophagy in FLT3-ITD mutated protein].
Zhonghua Xue Ye Xue Za Zhi
; 41(10): 836-842, 2020 Oct 14.
Article
em Zh
| MEDLINE
| ID: mdl-33190441
ABSTRACT
Objective:
Endoplasmic reticulum stress(ERS)was used as the research emphasis to further investigate the mechanisms of apoptosis of FLT3-ITD-mutated leukemia cells and decreased expression of FLT3-ITD mutated protein induced by all-trans retinoic acid(ATRA).Methods:
FLT3-ITD-mutated leukemia cell lines(MV4-11 and MOLM13)were treated with ATRA. Flow cytometry was conducted to assess cell apoptosis. Real-time fluorescent quantitative PCR(RT-qPCR)and Western blot were used to detect the expression of ERS-related and autophagy-related genes and protein, respectively.Results:
A low-dose ATRA further increased FLT3-ITD cells and ERS levels. ATRA acted on the ERS-related PERK/eif2É signaling pathway and continued to increase the ERS of FLT3-ITD cells, resulting in an upregulation of apoptotic gene CHOP expression. After the treatment with ATRA, FLT3-ITD protein in FLT3-ITD cells was decreased. Of the two main ERS-related protein degradation pathways, ER-associated degradation(ERAD)and ER-activated autophagy(ERAA), the expression of ERAD-related protein ATF6 in FLT3-ITD cells was not significantly changed on ATRA, whereas the expression of ERAA-related proteins Atg7 and Atg5 were significantly increased.Conclusions:
ATRA further raises the ERS level of FLT3-ITD cells continuously by activating the ERS-related PERK/eif2É signal pathway and induces FLT3-ITD protein autophagy degradation through ERAA pathway, which induces apoptosis of FLT3-ITD-mutated leukemia cells. These results provide preliminary evidence on the use of ATRA in the treatment of refractory leukemia with FLT3-ITD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse do Retículo Endoplasmático
Limite:
Humans
Idioma:
Zh
Revista:
Zhonghua Xue Ye Xue Za Zhi
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China