Cdc37 Contributes to bortezomib resistance in multiple myeloma via autophagy
10.3760/cma.j.issn.0253-2727.2020.07.009
- VernacularTitle:Cdc37调控细胞自噬参与骨髓瘤细胞对硼替佐米耐药的研究
- Author:
Lanting LIU
1
;
Shuhui DENG
;
Meirong ZANG
;
Jinqiao ZHANG
;
Lugui QIU
Author Information
1. 中国医学科学院血液病医院（中国医学科学院血液学研究所），实验血液学国家重点实验室，国家血液系统疾病临床医学研究中心，天津 300020
- Keywords:
Cdc37;
Cell autophagy;
Multiple myeloma;
Bortezomib resistance
- From:
Chinese Journal of Hematology
2020;41(7):583-588
- CountryChina
- Language:Chinese
-
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.
