DCZ3301, a novel cytotoxic agent, inhibits proliferation in diffuse large B-cell lymphoma via the STAT3 pathway
文献类型：期刊论文
| 作者 | Sun, Xi1,3; Li, Bo2; Xie, Bingqian3; Xu, Zhijian2 ; Chang, Gaomei3; Tao, Yi3; Zhang, Yong2; Chang, Shuaikang3; Wang, Yingcong3; Yu, Dandan3
|
| 刊名 | CELL DEATH & DISEASE
 |
| 出版日期 | 2017-10 |
| 卷号 | 8 |
| ISSN号 | 2041-4889 |
| DOI | 10.1038/cddis.2017.472 |
| 文献子类 | Article |
| 英文摘要 | Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in adults, characterized by a rapidly increasing painless mass. A novel compound, DCZ3301, was synthesized that exerted direct cytotoxicity against DLBCL cell lines. The effects of DCZ3301 on DLBCL cells in vitro and in vivo and the associated mechanisms were investigated. DCZ3301 inhibited the viability of DLBCL cell lines, even in the presence of protumorigenesis cytokines. Additionally, the compound induced apoptosis and cell cycle arrest at the G2/M phase by reducing mitochondrial membrane potential. DCZ3301 exerted an antitumor effect through modulation of Akt, extracellular signal-regulated kinases 1/2 (ERK1/2) and janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. Furthermore, DCZ3301 downregulates STAT3 phosphorylation by inhibiting Lck/Yes-related novel protein tyrosine kinase (Lyn) activation in DLBCL. A synergistic cytotoxic effect on DLBCL cells was observed upon combination of DCZ3301 with panobinostat. In vivo, intraperitoneal injection of xenograft mice with DCZ3301 resulted in reduced tumor volume. Our preliminary results collectively support the utility of the small-molecule inhibitor DCZ3301 as an effective novel therapeutic option for DLBCL that requires further clinical evaluation. |
| WOS关键词 | PROTEIN-TYROSINE KINASE ; HEMATOPOIETIC-CELLS ; SIGNALING PATHWAY ; CYCLE ARREST ; R-CHOP ; ACTIVATION ; APOPTOSIS ; LYN ; EXPRESSION ; SURVIVAL |
| 资助项目 | National Natural Science Foundation of China[81372391] ; National Natural Science Foundation of China[81570190] ; National Natural Science Foundation of China[81670194] ; National Natural Science Foundation of China[81529001] ; National Natural Science Foundation of China[81600174] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000414022900048 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272463]  |
| 专题 | 药物发现与设计中心 |
| 通讯作者 | Shi, Jumei; Zhu, Weiliang |
| 作者单位 | 1.Nanjing Med Univ, Sch Clin Med, Nanjing 210000, Jiangsu, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 3.Tongji Univ, Sch Med, Canc Ctr, Shanghai Peoples Hosp 10,Dept Hematol, 301 Yanchang Rd, Shanghai 200072, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Sun, Xi,Li, Bo,Xie, Bingqian,et al. DCZ3301, a novel cytotoxic agent, inhibits proliferation in diffuse large B-cell lymphoma via the STAT3 pathway[J]. CELL DEATH & DISEASE,2017,8. |
| APA | Sun, Xi.,Li, Bo.,Xie, Bingqian.,Xu, Zhijian.,Chang, Gaomei.,...&Zhu, Weiliang.(2017).DCZ3301, a novel cytotoxic agent, inhibits proliferation in diffuse large B-cell lymphoma via the STAT3 pathway.CELL DEATH & DISEASE,8. |
| MLA | Sun, Xi,et al."DCZ3301, a novel cytotoxic agent, inhibits proliferation in diffuse large B-cell lymphoma via the STAT3 pathway".CELL DEATH & DISEASE 8(2017). |
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。