IL-6 Regulates the Chemosensitivity of Drug-Resistant Multiple Myeloma Cell Lines to Bortezomib through STAT3/Notch Signaling Pathway.
10.19746/j.cnki.issn.1009-2137.2022.05.026
- Author:
Ying LIU
1
,
2
;
Jing-Zhe SUI
2
,
3
;
Li-Hua ZHU
2
,
4
;
Yi DAI
5
;
Hai-Qun DONG
5
;
Peng CHENG
1
,
6
Author Information
1. Department of Hematology, The First Affiliated Hospital of Guangxi Medical University
2. Nanning 530021, Guangxi Zhuang Autonomous Region, China.
3. Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University
4. Department of Health Management, The First Affiliated Hospital of Guangxi Medical University
5. The First Clinical Medical College of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
6. Nanning 530021, Guangxi Zhuang Autonomous Region, China.E-mail: 116355732@qq.com.
- Publication Type:Journal Article
- Keywords:
bortezomib;
chemosensitivity;
interleukin-6;
multiple myeloma
- MeSH:
Antibodies, Neutralizing/therapeutic use*;
Apoptosis;
Bortezomib/therapeutic use*;
Cell Line, Tumor;
Cell Proliferation;
Humans;
Interleukin-6/metabolism*;
Multiple Myeloma/drug therapy*;
RNA, Messenger;
STAT3 Transcription Factor/metabolism*;
Signal Transduction;
Sincalide/therapeutic use*
- From:
Journal of Experimental Hematology
2022;30(5):1474-1481
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of interleukin-6 (IL-6) on the chemosensitivity of drug-resistant multiple myeloma (MM) cell lines to bortezomib (BTZ) and its mechanism.
METHODS:Peripheral blood samples were collected from patients with BTZ-resistant MM before and after treatment. Human MM cell lines KM3 and KM3/BTZ were cultured in vitro. ELISA was used to detect the content of IL-6 in peripheral blood of MM patients, KM3 and KM3/BTZ cells. CCK-8 assay was used to detect the drug sensitivity of KM3 and KM3 / BTZ cells to BTZ. KM3 / BTZ cells were divided into KM3/BTZ control group (normal culture for 48 h), IL-6 neutralizing antibody Anti-IL-6 group (500 ng/ml Anti-IL-6 treated for 48 h), BTZ group (300 ng/ml BTZ treated for 48 h), BTZ + Anti-IL-6 group (300 ng/ml BTZ and 500 ng/ml Anti-IL-6 treated for 48 h). The proliferation activity of KM3 / BTZ cells was detected by CCK-8 assay. The cell cycle distribution of KM3/BTZ cells was detected by flow cytometry. The apoptosis of KM3/BTZ cells was detected by Annexin V-FITC/PI double staining. The mRNA expression levels of IL-6, Notch1, signal transducer and activator of transcription 3 (STAT3) in KM3/BTZ cells were detected by real-time fluorescent quantitative PCR (qRT-PCR), and the protein expression levels of IL-6, Notch1, STAT3 in KM3/BTZ cells were detected by Western blot.
RESULTS:The level of IL-6 in peripheral blood of patients with BTZ-resistant MM after treatment was significantly higher than that before treatment (P<0.05). The level of IL-6 in KM3/BTZ cells was significantly higher than that in KM3 cells (P<0.05). The sensitivity of KM3/BTZ cells to BTZ was significantly lower than that of KM3 cells (P<0.05), and the resistance index (RI) was 19.62. Anti-IL-6 and BTZ could inhibit the proliferation of KM3 / BTZ cells, block cell cycle, and induce apoptosis (P<0.05). Compared with single drug treatment, the combined effect of Anti-IL-6 and BTZ was more obvious on KM3/BTZ cells (P<0.05), and significantly down regulated the mRNA and protein expression of IL-6, Notch1 and STAT3 in KM3/BTZ cells (P<0.05).
CONCLUSION:Antagonizing IL-6 can increase the chemosensitivity of MM cells to BTZ, and IL-6 may reduce the sensitivity of MM cells to BTZ through STAT3/Notch signaling pathway.
