Exploring the mechanism of elemene synergistic bortezomib against multiple myeloma by ROS-NF-κB-p38MAPK pathway
10.12092/j.issn.1009-2501.2023.11.003
- Author:
Ruifang ZHU
1
;
Dongkai GUO
1
;
Hui ZHI
1
;
Yiguo JIANG
1
;
Yueling ZHANG
1
;
Xiaoping QIAN
1
;
Shiliang JI
1
Author Information
1. Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing University Medical School
- Publication Type:Journal Article
- Keywords:
apoptosis;
elemene;
multiple myeloma;
ROS/NF-κB/p38 MAPK signaling pathway
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2023;28(11):1219-1226
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the mechanism of elemene synergistic bortezomib against multiple myeloma based on ROS-NF-κB-p38MAPK signaling pathway. METHODS: CCK-8 assay was used to detect cell activity. Nude mice were randomly divided into control group, bortezomib (BTZ) group, elemene (ELE) group and combination group. Each group was treated with BTZ, ELE and BTZ combined with ELE, respectively. Tunel staining was performed to observe the apoptosis of tumor tissues. The expressions of Caspase-3, Bcl-2, NF-κB and p38 MAPK were detected by Western Blot. Cell cycle, apoptosis and reactive oxygen species (ROS) expression were detected by flow cytometry using human myeloma U266 cells. RESULTS: When 4.0 μmol/L ELE combined with 50 nmol/L BTZ treated U266, the cell activity was significantly reduced compared with that of NC, BTZ and ELE groups (P< 0.05). The tumor volume of nude mice in BTZ group, ELE group and combined group was significantly reduced compared with the control group (P <0.05), and the combined group was the smallest. Tunel staining results showed that the apoptosis level in the control group was lower than that in the BTZ group, ELE group and the combined group (P<0.05), and the combined group had the lowest apoptosis level. Compared with the control group, the expressions of Caspase-3 and p38 MAPK in BTZ group, ELE group and combination group were significantly increased, while the expression of Bcl-2 was significantly decreased. The apoptosis level and expression of ROS in BTZ group, ELE group and the combined group was significantly increased compared with the control group (P<0.05). CONCLUSION: ELE can enhance the role of BTZ in promoting apoptosis of myeloma cells, which may be achieved by regulating ROS/NF-κB/p38 MAPK signaling pathway to enhance the level of apoptosis of tumor cells to achieve anti-tumor effect.
