中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Dihydrocelastrol induces antitumor activity and enhances the sensitivity of bortezomib in resistant multiple myeloma by inhibiting STAT3-dependent PSMB5 regulation

文献类型：期刊论文

作者Jin, Shuhan1; Li, Bo2; Zhang, Bibo1,4; Gao, Xuejie1; Jia, Xinyan1; Xu, Li1; Chang, Shuaikang1; Hu, Ke1; Wang, Guanli1; Xu, Zhijian2
刊名ACTA BIOCHIMICA ET BIOPHYSICA SINICA
出版日期2023-12-01
卷号55期号:12页码:1884-1891
ISSN号1672-9145
关键词dihydrocelastrol multiple myeloma JAK2/STAT3 PSMB5 bortezomib resistance
DOI10.3724/abbs.2023260
通讯作者Shi, Jumei(shijumei@tongji.edu.cn) ; Zhu, Weiliang(wlzhu@simm.ac.cn) ; Chen, Gege(m18767221930@163.com)
英文摘要Multiple myeloma (MM) is characterized by excessive aggregation of B-cell-derived malignant plasma cells in the hematopoietic system of bone marrow. Previously, we synthesized an innovative molecule named dihydrocelastrol (DHCE) from celastrol, a triterpene purified from medicinal plant Tripterygium wilfordii. Herein, we explore the therapeutic properties and latent signal transduction mechanism of DHCE action in bortezomib (BTZ)-resistant (BTZ-R) MM cells. In this study, we first report that DHCE shows antitumor activities in vitro and in vivo and exerts stronger inhibitory effects than celastrol on BTZ-R cells. We find that DHCE inhibits BTZ-R cell viability by promoting apoptosis via extrinsic and intrinsic pathways and suppresses BTZ-RMMcell proliferation by inducing G0/G1 phase cell cycle arrest. In addition, inactivation of JAK2/STAT3 and PI3K/Akt pathways are involved in the DHCE-mediated antitumor effect. Simultaneously, DHCE acts synergistically with BTZ on BTZ-R cells. PSMB5, a molecular target of BTZ, is overexpressed in BTZ-R MM cells compared with BTZ-S MM cells and is demonstrated to be a target of STAT3. Moreover, DHCE downregulates PSMB5 overexpression in BTZ-R MM cells, which illustrates that DHCE overcomes BTZ resistance through increasing the sensitivity of BTZ in resistant MM via inhibiting STAT3-dependent PSMB5 regulation. Overall, our findings imply that DHCE may become a potential therapeutic option that warrants clinical evaluation for BTZ-R MM.
WOS关键词PROTEASOME INHIBITOR ; IN-VITRO ; APOPTOSIS ; PROLIFERATION ; CELLS ; OVEREXPRESSION ; CELASTROL
资助项目National Natural Science Foundation of China[81971529] ; National Natural Science Foundation of China[81900212] ; National Natural Science Foundation of China[82170200] ; National Natural Science Foundation of China[82070224] ; National Natural Science Foundation of China[81900210] ; National Natural Science Foundation of China[81900207]
WOS研究方向Biochemistry & Molecular Biology ; Biophysics
语种英语
出版者SCIENCE PRESS
WOS记录号WOS:001143834200004
源URL[http://119.78.100.183/handle/2S10ELR8/308915]  
专题新药研究国家重点实验室
通讯作者Shi, Jumei; Zhu, Weiliang; Chen, Gege
作者单位1.Tongji Univ, Shanghai East Hosp, Dept Hematol, Sch Med, Shanghai 200120, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R China
3.Tongji Univ, Shanghai Peoples Hosp 10, Dept Hematol, Sch Med, Shanghai 200072, Peoples R China
4.Ningbo Univ, Dept Hematol, Affiliated Peoples Hosp, Ningbo 315000, Peoples R China
推荐引用方式
GB/T 7714		 Jin, Shuhan,Li, Bo,Zhang, Bibo,et al. Dihydrocelastrol induces antitumor activity and enhances the sensitivity of bortezomib in resistant multiple myeloma by inhibiting STAT3-dependent PSMB5 regulation[J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA,2023,55(12):1884-1891.
APA Jin, Shuhan.,Li, Bo.,Zhang, Bibo.,Gao, Xuejie.,Jia, Xinyan.,...&Chen, Gege.(2023).Dihydrocelastrol induces antitumor activity and enhances the sensitivity of bortezomib in resistant multiple myeloma by inhibiting STAT3-dependent PSMB5 regulation.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,55(12),1884-1891.
MLA Jin, Shuhan,et al."Dihydrocelastrol induces antitumor activity and enhances the sensitivity of bortezomib in resistant multiple myeloma by inhibiting STAT3-dependent PSMB5 regulation".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 55.12(2023):1884-1891.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。