Effect of Celastrol Based on IRAK4/ERK/p38 Signaling Pathway on Proliferation and Apoptosis of Multiple Myeloma Cells.
10.19746/j.cnki.issn.1009-2137.2022.01.029
- Author:
Xiao-Meng XU
1
,
2
;
Di KANG
3
;
Xin-Yu ZHU
1
,
2
;
Xiang-Tu KONG
1
,
4
;
Hui YU
1
,
4
;
Xiao-Li CHEN
1
,
4
;
Peng-Jun JIANG
1
,
4
;
Hai-Wen NI
1
,
5
Author Information
1. Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine
2. Nanjing 210029, Jiangsu Province, China,First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China.
3. First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China,E-mail: kangdi@njucm.edu.cn.
4. Nanjing 210029, Jiangsu Province, China.
5. Nanjing 210029, Jiangsu Province, China,E-mail: fsyy00654@njucm.edu.cn.
- Publication Type:Journal Article
- Keywords:
ARP-1;
H929;
IRAK4/ERK/p38 signaling pathway;
bortezomib;
celastrol;
multiple myeloma
- MeSH:
Apoptosis;
Bortezomib/pharmacology*;
Cell Line, Tumor;
Cell Proliferation;
Humans;
Interleukin-1 Receptor-Associated Kinases;
Multiple Myeloma;
Pentacyclic Triterpenes;
Signal Transduction
- From:
Journal of Experimental Hematology
2022;30(1):175-182
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of celastrol on the proliferation and apoptosis of human multiple myeloma (MM) cell lines, reveal the relationship between IRAK4/ERK/p38 signaling pathway and celastrol regulating the proliferation and apoptosis of H929 and ARP-1 cells, and explore whether celastrol combined with bortezomib has synergistic effect.
METHODS:CCK-8 method was used to detect the viability of MM cell lines H929 and ARP-1 treated by different concentrations of celastrol, bortezomib, and their combination, and the synergistic effect was determined by Kim's formula. The apoptosis rate of H929 cells and necrosis rate of ARP-1 were detected by Annexin V/PI method. The expression of key proteins and apoptosis proteins in IRAK4/ERK/p38 signaling pathway were detected by Western blot.
RESULTS:Celastrol could significantly inhibit the proliferation of H929 and ARP-1 cells (r=0.9018, r=0.9244) and induce apoptosis in a time-dependent manner. Compared with the control group, celastrol could significantly up-regulate the expression of PARP and cleaved caspase-3 while down-regulate the expression of p-IRAK4, p-ERK, and p-p38 in H929 and ARP-1 cells. Celastrol and bortezomib alone inhibited the proliferation of H929 and ARP-1 cells. Compared with celastrol and bortezomib alone, their combination had lower cell survival rate and higher apoptosis rate (P<0.05).
CONCLUSION:Celastrol can inhibit the proliferation and promote the apoptosis of H929 and ARP-1 cells, which may be related to inhibiting the phosphorylation of IRAK4 and blocking the activation of IRAK4/ERK/p38 signaling pathway. Celastrol combined with bortezomib has synergistic effect, which can more effectively inhibit the proliferation and induce apoptosis of H929 and ARP-1 cells.
