[Cdc37 Contributes to bortezomib resistance in multiple myeloma via autophagy].
Zhonghua Xue Ye Xue Za Zhi
; 41(7): 583-588, 2020 Jul 14.
Article
em Zh
| MEDLINE
| ID: mdl-32810966
ABSTRACT
Objective:
To explore the role of cell division cycle protein 37 (Cdc37) mediating bortezomib (BTZ) resistance in multiple myeloma (MM) via the regulation of autophagy activity to provide a novel strategy for MM therapy.Methods:
The expressions of Cdc37 and LC3b were investigated in BTZ-resistant MM cell line ANBL-6.BR using quantitative real-time PCR (qRT-PCR) and western blot (WB) analysis. Cdc37 was upregulated in ANBL-6.BR cells owing to lentivirus transfection. The LC3b expression was detected with WB, and BTZ-induced apoptosis was explored using flow cytometry. Cdc37 was then down-regulated by shRNA in the MM cell line NCI-H929. Sensitivity of BTZ was evaluated using CCK-8 analysis. WB analysis was performed to check the expression of the AKT/mTOR pathway and autophagy-associated proteins. The sensitivity of NCI-H929 cells to BTZ in the presence of autophagy inhibitor chloroquine (CQ) was analyzed using flow cytometry.Results:
Cdc37 was down-regulated, while autophagy-associated gene LC3b was upregulated in BTZ-resistant cell line ANBL-6.BR. Up-regulated Cdc37 in ANBL-6.BR cells could inhibit LC3b expression and increase the sensitivity of MM to BTZ. Suppressing Cdc37 expression in MM cell line NCI-H929 induced BTZ resistance and autophagy activation, while CQ could rescue BTZ resistance caused by Cdc37 inhibition.Conclusion:
Cdc37 may participate in BTZ resistance in MM via the regulation of autophagy activity.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Mieloma Múltiplo
Limite:
Humans
Idioma:
Zh
Revista:
Zhonghua Xue Ye Xue Za Zhi
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China