Anti-DLBCL efficacy of DCZ0825 in vitro and in vivo: involvement of the PI3K-AKT-mTOR/JNK pathway
文献类型：期刊论文
| 作者 | Hu, Ke1,3; Li, Bo2; Ma, Ruye3; Yi, Hongfei3; Xu, Zhijian2 ; Peng, Yu3; Yu, Dandan3; Wu, Huiqun3; Cheng, Taofang3; Lu, Yumeng3
|
| 刊名 | ACTA BIOCHIMICA ET BIOPHYSICA SINICA
 |
| 出版日期 | 2021-05-01 |
| 卷号 | 53期号:5页码:575-583 |
| 关键词 | caspase cell proliferation cell cycle arrest diffuse large B-cell lymphoma PI3K-AKT-mTOR/JNK pathway |
| ISSN号 | 1672-9145 |
| DOI | 10.1093/abbs/gmab031 |
| 通讯作者 | Zhu, Weiliang(wlzhu@simm.ac.cn) ; Shi, Jumei(shijumei@tongji.edu.cn) |
| 英文摘要 | Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, characterized by high heterogeneity. The poor outcome of a portion of patients who suffer relapsing or resistant to conventional treatment impels the development of novel agents for DLBCL. DCZ0825 is a novel compound derived from pterostilbene and osalmide, whose antitumor activities have drawn our attention. In this study, we found that DCZ0825 exhibited high cytotoxicity toward DLBCL cell lines in a dose- and time-dependent manner, as revealed by cell counting kit-8 assay. Flow cytometry and western blot analysis results showed that DCZ0825 also promoted cell apoptosis via both extrinsic and intrinsic apoptosis pathways mediated by caspase. In addition, DCZ0825 induced cell cycle arrest in the G2/M phase by downregulating Cdc25C, CDK1, and Cyclin B1, thus interfering with cell proliferation. Further investigation showed the involvement of the phosphatidylinositol 3-kinase (PI3K)-AKT-mTOR/JNK pathway in the efficacy of DCZ0825 against DLBCL. Remarkably, DCZ0825 also exerted notable cytotoxic effects in vivo as well, with low toxicity to important internal organs such as the liver and kidney. Our results suggest that DCZ0825 may have the potential to become a novel anti-DLBCL agent or to replenish the conventional therapeutic scheme of DLBCL. |
| WOS关键词 | AKT INHIBITORS ; APOPTOSIS ; CELLS ; MTOR ; PERIFOSINE ; ARREST |
| 资助项目 | National Natural Science Foundation of China[81870158] ; National Natural Science Foundation of China[81670194] ; National Natural Science Foundation of China[81900210] ; Natural Science Foundation of Shanghai, China[19ZR1467800] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics |
| 语种 | 英语 |
| WOS记录号 | WOS:000647744900007 |
| 出版者 | OXFORD UNIV PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/296674]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhu, Weiliang; Shi, Jumei |
| 作者单位 | 1.Nanjing Med Univ, Sch Clin Med, Nanjing 211100, Peoples R China 2.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 3.Tongji Univ, Shanghai Peoples Hosp 10, Dept Hematol, Sch Med, Shanghai 200072, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hu, Ke,Li, Bo,Ma, Ruye,et al. Anti-DLBCL efficacy of DCZ0825 in vitro and in vivo: involvement of the PI3K-AKT-mTOR/JNK pathway[J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA,2021,53(5):575-583. |
| APA | Hu, Ke.,Li, Bo.,Ma, Ruye.,Yi, Hongfei.,Xu, Zhijian.,...&Shi, Jumei.(2021).Anti-DLBCL efficacy of DCZ0825 in vitro and in vivo: involvement of the PI3K-AKT-mTOR/JNK pathway.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,53(5),575-583. |
| MLA | Hu, Ke,et al."Anti-DLBCL efficacy of DCZ0825 in vitro and in vivo: involvement of the PI3K-AKT-mTOR/JNK pathway".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 53.5(2021):575-583. |
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。