Cyclin-dependent kinase 7/9 inhibitor SNS-032 induces apoptosis in diffuse large B-cell lymphoma cells. Issue 1 (31st December 2022)

• Record Type: Journal Article
• Authors: Jiang, Liling; Wen, Chuangyu; Zhou, Huan; Liu, Aochu; Zhang, Haichuan; Chen, Xinmei; Ding, Wa; Liu, Jinbao; Shi, Xianping
• Is Part Of: Cancer biology & therapy. Volume 23:Issue 1(2022)
• Page Start: 319
• Page End: 327
• Publication Date: 2022-12-31
• Subjects: SNS-032 -- apoptosis -- diffuse large B-cell lymphoma -- chemotherapy -- cyclin-dependent kinase 7/9; 616.99406
• DOI: 10.1080/15384047.2022.2055421
• Languages: English
• ISSNs: 1538-4047

Abstract

ABSTRACT: Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) are refractory or relapse to standard chemotherapy, and most of them are activated B cell-like DLBCLs (ABC-DLBCL) and germinal center B cell-like DLBCLs (GCB-DLBCL). SNS-032, a novel and selective CDK7/9 inhibitor, that the first phase clinical trials approved by US FDA for cancer treatment have been completed. In this study, we investigated the anti-tumor effect of SNS-032 in ABC- and GCB-DLBCL subtypes. We report that SNS-032 induced growth inhibition and cell apoptosis in both DLBCL cells in vitro, and inhibited the growth of both DLBCL xenografts in nude mice. Mechanistically, SNS-032 inhibited RNA polymerase II, which led to transcriptional-dependent suppression of NF-κB signaling pathway and its downstream targets involved in cell survival; SNS-032 also downregulates BCL-2 and c-MYC in both mRNA and protein levels. Significantly, these findings provide pre-clinical evidence for application of targeting the CDK7/9 in DLBCL.