Bafetinib Suppresses the Transcription of PD-L1 Through c-Myc in Lung Cancer

被引:3
作者
Chen, Xi [1 ]
Du, Qianqian [1 ]
Guo, Hongjie [1 ]
He, Qiaojun [1 ,2 ]
Yang, Bo [1 ,2 ]
Ding, Ling [1 ]
机构
[1] Zhejiang Univ, Inst Pharmacol & Toxicol, Coll Pharmaceut Sci, Zhejiang Prov Key Lab Anticanc Drug Res, Hangzhou, Peoples R China
[2] Zhejiang Univ, Innovat Inst Artificial Intelligence Med, Hangzhou, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
bafetinib; c-Myc; PD-L1; transcription; lung cancer; DNA-BINDING; INHIBITION; PROMOTES; IMATINIB; LYN; BLOCKADE; TARGET; NS-187; CELLS; MAX;
D O I
10.3389/fphar.2022.897747
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Given the limitations of the existing antibody-based therapies, including immune-related adverse events, poor response rates, and intravenous route of dosing, small molecules inhibitors targeting PD-L1 are highly desirable. By cell-based screening, we found that tyrosine kinase inhibitor Bafetinib dramatically suppresses PD-L1 protein expression in a dose-dependent manner. In parallel, cell membrane PD-L1 is also reduced by Bafetinib. We confirm that Bafetinib doesn't affect the protein half-life of PD-L1 but significantly inhibits the transcription of PD-L1. Among the transcription factors that regulate PD-L1 expression, c-Myc is downregulated by Bafetinib. Bafetinib caused PD-L1 inhibition is abolished when c-Myc is knocked-down. Further, we identified that Bafetinib reduced c-Myc expression because of transcription inhibition. By using the CT26 tumor model, we further confirm that Bafetinib suppressed PD-L1 expression in vivo. In conclusion, our study shows that Bafetinib inhibits the transcription of PD-L1 through transcription factor c-Myc, suggesting that Bafetinib might be a small molecule drug targeting PD-L1.
引用
收藏
页数:9
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