The Inhibiting Effect of Autophagy Inhibitor ROC-325 on Multiple Myeloma.
10.19746/j.cnki.issn.1009-2137.2021.03.023
- Author:
Meng-Ya SHI
1
,
2
;
Yao YAO
1
,
2
;
Ju DENG
1
,
2
;
Can-Li YUAN
1
,
2
;
Hui-Min LIU
1
,
2
;
Zhen-Yu LI
1
,
3
Author Information
1. Institute of Hematology, Xuzhou Medical University
2. Department of Hematology, Xuzhou Medical University Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China.
3. Department of Hematology, Xuzhou Medical University Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China,E-mail: lizhenyumd@163.com.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
Autophagy;
Bortezomib/pharmacology*;
Cell Line, Tumor;
Cell Proliferation;
Humans;
Hydroxychloroquine/analogs & derivatives*;
Multiple Myeloma
- From:
Journal of Experimental Hematology
2021;29(3):797-804
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effects of autophagy inhibitor ROC-325 and its combination with bortezomib on the proliferation, apoptosis and autophagy of multiple myeloma cell lines.
METHODS:Multiple myeloma cells were treated with ROC-325 at different concentration. The cell proliferation was detected by CCK-8. Apoptosis was determined by Caspase-3/7 and Caspase-9 activity assays. Autophagy was detected by monodansylcadaverine staining. The apoptosis-related proteins (PARP and Caspase-3) and autophagy-related proteins (P62, Beclin-1, and LC3A/B) were analyzed by Western blot. The combined effect with bortezomib on bortezomib-resistant cell line was detected by CCK-8.
RESULTS:ROC-325 inhibited the proliferation of RPMI 8226, RPMI 8226-BTZ100, U266 and IM9 cells in a dose-dependent manner (r=-0.8275, r=-0.9079, r=-0.9422, r=-0.9305), the 72 h IC
CONCLUSION:ROC-325 can inhibit the proliferation, induce the apoptosis of myeloma cells through the mitochondrial pathway, inhibit the autophagy of myeloma cells by affecting the fusion of autophagosomes and lysosomes, and overcome bortezomib resistance by the combination of ROC-325 with bortezomib.
