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A novel silicone derivative of natural osalmid (DCZ0858) induces apoptosis and cell cycle arrest in diffuse large B-cell lymphoma via the JAK2/STAT3 pathway

文献类型：期刊论文

作者Lu, Kang1,3; Li, Bo2; Zhang, Hui1; Xu, Zhijian2; Song, Dongliang1; Gao, Lu1; Sun, Haiguo2; Li, Liping1; Wang, Yingcong1; Feng, Qilin1
刊名SIGNAL TRANSDUCTION AND TARGETED THERAPY
出版日期2020-04-01
卷号5期号:1页码:11
ISSN号2095-9907
DOI10.1038/s41392-020-0123-0
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 a highly heterogeneous malignant tumor characterized by diffuse growth. DCZ0858 is a novel small molecule with excellent antitumor effects in DLBCL. This study explored in depth the inhibitory effect of DCZ0858 on DLBCL cell lines. Cell Counting Kit-8 (CCK-8) and plate colony formation assays were used to evaluate cell proliferation levels. Flow cytometry was employed to analyze apoptosis and the cell cycle, and western blotting was used to quantify the expression of cell cycle regulators. The results indicated that DCZ0858 inhibited cell growth in a concentration-dependent and time-dependent manner while inducing no significant toxicity in normal cells. Moreover, DCZ0858 initiated cell apoptosis via both internal and external apoptotic pathways. DCZ0858 also induced cell cycle arrest in the G0/G1 phase, thereby controlling cell proliferation. Further investigation of the molecular mechanism showed that the JAK2/STAT3 pathway was involved in the DCZ0858-mediated antitumor effects and that JAK2 was the key target for DCZ0858 treatment. Knockdown of JAK2 partly weakened the DCZ0858-mediated antitumor effect in DLBCL cells, while JAK2 overexpression strengthened the effect of DCZ0858 in DLBCL cells. Moreover, a similar antitumor effect was observed for DCZ0858 and the JAK2 inhibitor ruxolitinib, and combining the two could significantly enhance cancer-suppressive signaling. Tumor xenograft models showed that DCZ0858 inhibited tumor growth in vivo and had low toxicity in important organs, findings that were consistent with the in vitro data. In summary, DCZ0858 is a promising drug for the treatment of DLBCL.
WOS关键词GENE-EXPRESSION ; STAT3 ; SURVIVAL ; PROLIFERATION ; INHIBITION ; ACTIVATION
资助项目National Natural Science Foundation of China[81529001] ; National Natural Science Foundation of China[81570190] ; National Natural Science Foundation of China[81670194] ; National Natural Science Foundation of China[81870158] ; National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China[2018ZX09711002]
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000523113600001
源URL[http://119.78.100.183/handle/2S10ELR8/280933]  
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.Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Hematol, Shanghai 200072, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China
3.Nantong Univ, Sch Med, Nantong 226001, Peoples R China
推荐引用方式
GB/T 7714		 Lu, Kang,Li, Bo,Zhang, Hui,et al. A novel silicone derivative of natural osalmid (DCZ0858) induces apoptosis and cell cycle arrest in diffuse large B-cell lymphoma via the JAK2/STAT3 pathway[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2020,5(1):11.
APA Lu, Kang.,Li, Bo.,Zhang, Hui.,Xu, Zhijian.,Song, Dongliang.,...&Shi, Jumei.(2020).A novel silicone derivative of natural osalmid (DCZ0858) induces apoptosis and cell cycle arrest in diffuse large B-cell lymphoma via the JAK2/STAT3 pathway.SIGNAL TRANSDUCTION AND TARGETED THERAPY,5(1),11.
MLA Lu, Kang,et al."A novel silicone derivative of natural osalmid (DCZ0858) induces apoptosis and cell cycle arrest in diffuse large B-cell lymphoma via the JAK2/STAT3 pathway".SIGNAL TRANSDUCTION AND TARGETED THERAPY 5.1(2020):11.

入库方式： OAI收割

来源：上海药物研究所

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