Effects of Decitabine Combined with Bortezomib on the Proliferation of Mantle Cell Lymphoma Cell Lines and Its Underling Mechanisms.
10.19746/j.cnki.issn.1009-2137.2020.04.019
- Author:
Jing-Nan ZHANG
1
;
Shu-Kai QIAO
1
;
Dan CHEN
1
;
Li-Na XING
1
;
Yang LI
1
;
Xiao-Nan GUO
2
Author Information
1. Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province，China.
2. Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province，China,E-mail: guoxiaonan0108@163.com.
- Publication Type:Journal Article
- MeSH:
Adult;
Apoptosis;
Bortezomib;
Cadherins;
Cell Line, Tumor;
Cell Proliferation;
Decitabine;
Humans;
Lymphoma, Mantle-Cell
- From:
Journal of Experimental Hematology
2020;28(4):1197-1204
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effects of decitabine combined with bortezomib on the proliferation of mantle cell lymphoma cell lines (Jeko-1 and Grante519) in vitro and explore the underlying mechanisms.
METHODS:Jeko-1 and Grante519 cells were treated with different concentrations of decitabine and/or bortezomib alone and their combination.The cell proliferation was determined by CCK-8 assay. the cell apoptosis were detected by flow cytometry, the mRNA and protein expression levels of genes related with the cell cycle and apoptosis were analyzed by RT-PCR and Western blot respactively.
RESULTS:Low dose DAC could significantly inhibit the proliferation and induce apoptosis of Jeko-1 and Grante519 cells which shows a dose-and time-dependent manner. After DAC treatment, caspase 3, BAX and PCDH8 expression levels increased, while BCL-2 and CCND1 expression levels decreased in Jeko-1 and Grante519 cells, but there was no significant difference in NF-κB expression. High dose BTZ could significantly inhibit the proliferation and induce apoptosis of Jeko-1 and Grante519 cells which shows a dose-and time-dependent manner; single drug BTZ could increase the expression level of Caspase 3 and BAX, and decrease the expression level of NF-κB, BCL-2 and CCDN1 in Jeko-1 and Grante519 cells, but there was significant difference in PCDH8 expression level. Compared with single-drug treatment group, DAC combined with BTZ significantly increased the inhibitory rate and apoptotic rate of Jeko-1 and Grante519 cells; PCDH8, Caspase 3 and BAX expression levels significantly increased, and the expression levels of NF-κB, BCL-2 and CCND1 significantly decreased in Jeko-1 and Grante519 cells.
CONCLUSION:The combination of DAC and BTZ has obviously synergistic effects on the growth inhibition of Jeko-1 and Grante519 cells which maybe relates with enhancing inbibitory effect on NF-κB signal pathway, down-regulating BAX expression, up-regulating BAX expression as well as increasing cospase 3 expression. This study provides a novel therapeutic approach for mantle cell lymphoma.
