Effect of Doxycycline on Intrinsic Apoptosis of Myeloma Cell Line H929 and Its Mechanism.
10.19746/j.cnki.issn.1009-2137.2022.02.020
- Author:
Hai-Lu LI
1
;
Xiao-Ming FEI
2
;
Yu TANG
3
;
Yuan-Lin YANG
1
;
Li-Xia WANG
1
;
Jia-Wei GENG
1
Author Information
1. Department of Hematology， The Affiliated Hospital of Jiangsu University， Zhenjiang 212000， Jiangsu Province， China.
2. Department of Hematology， The Affiliated Hospital of Jiangsu University， Zhenjiang 212000， Jiangsu Province， China,E-mail：feixiaomingujs@aliyun.com.
3. Department of Rheumatology， The Affiliated Hospital of Jiangsu University， Zhenjiang 212000， Jiangsu Province， China.
- Publication Type:Journal Article
- Keywords:
.multiple myeloma;
H929;
MEK/ERK pathway;
apoptosis;
c-Jun;
doxycycline
- MeSH:
Apoptosis;
Caspase 3;
Caspase 9/pharmacology*;
Cell Line, Tumor;
Cell Proliferation;
Doxycycline/pharmacology*;
Humans;
Mitogen-Activated Protein Kinase Kinases/pharmacology*;
Multiple Myeloma
- From:
Journal of Experimental Hematology
2022;30(2):441-448
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the mechanism of the in vitro toxicity of doxycycline to myeloma cell line H929 and also the possible pathway involved its toxicity.
METHODS:Myeloma cell line H929 was treated with DOX, MEK inhibitor U0126 or RAS agonist ML-098, either alone or in combination. Then, the expression of p-MEK, caspase-3, caspase-9 and c-Jun in H929 were used to detected by Western blot; the cells proliferation and apoptosis were detected by CCK-8 assay and flow cytometry, respectively.
RESULTS:DOX significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK in H929 (P<0.05). MEK antagonist U0126 significantly increased the levels of cleaved caspase-3 and caspase-9, and down-regulated the level of p-MEK (P<0.05). After Dox combined with ML-098 treatment of H929 cells, the apoptosis rate of H929 cells was lower than that of DOX alone treatment group(P<0.05). Compared with DOX alone treatment group, the expressions of p-MEK and p-ERK1/2 in DOX+ML-098 combined treatment group were increased, and the levels of cleaved caspase-3,9 in H929 cells were decreased (P<0.05). The levels of c-Jun mRNA and protein increased in H929 when treated by DOX alone (P<0.05).
CONCLUSION:DOX can induce apoptosis of H929 via intrinsic apoptosis pathway, and MEK/ERK pathway and c-Jun possibly play a role in this process.
