Anti-DLBCL efficacy of DCZ0825 in vitro and in vivo:involvement of the PI3K‒AKT‒mTOR/JNK pathway

查看全文 作　　者：Ke [1,2]Hu;Bo [3]Li;Ruye [1]Ma;Hongfei [1]Yi;Zhijian [3]Xu;Yu [1]Peng;Dandan [1]Yu;Huiqun [1]Wu;Taofang [1]Cheng;Yumeng [1]Lu;Yong [3]Zhang;Rong [1]Wei;Guang [1]Yang;Xiaosong [1]Wu;Weiliang [3]Zhu;Jumei [1]Shi

机构地区：[1]Department of Hematology,Shanghai Tenth People’s Hospital,Tongji University School of Medicine,Shanghai 200072,China;[2]Nanjing Medical University School of Clinical Medicine,Nanjing 211100,China;[3]CAS Key Laboratory of Receptor Research,Drug Discovery and Design Center,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China

出　　处：《Acta Biochimica et Biophysica Sinica》索引2021年第53卷第5期,共9页

基　　金：the grants from the National Natural Science Foundation of China(Nos.81870158,81670194,and 81900210);Natural Science Foundation of Shanghai,China(No.19ZR1467800). 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. 关键词：caspase cell proliferation cell cycle arrest diffuse large B-cell lymphoma PI3K−AKT−mTOR/JNK pathway

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Anti-DLBCL efficacy of DCZ0825 in vitro and in vivo:involvement of the PI3K‒AKT‒mTOR/JNK pathway

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