Berberine Derivative B68 Promotes Tumor Immune Clearance by Dual-Targeting BMI1 for Senescence Induction and CSN5 for PD-L1 Degradation
文献类型：期刊论文
| 作者 | Hu, Hongmei7; Wang, Qun7; Yu, Dianping7; Tao, Xiaoyu1,6; Guo, Mengmeng7; Tian, Saisai2; Zhang, Qing7; Xu, Mengting7; Geng, Xiangxin7; Zhang, Hongwei7 |
| 刊名 | ADVANCED SCIENCE
 |
| 出版日期 | 2024-12-25 |
| 页码 | 21 |
| 关键词 | BMI1 colorectal cancer CSN5 PD-L1 tumor cell senescence |
| DOI | 10.1002/advs.202413122 |
| 通讯作者 | Xu, Hanchen(hanson0702@126.com) ; Li, Bo(boli@simm.ac.cn) ; Zhang, Weidong(wdzhangy@hotmail.com) ; Liu, Sanhong(liush@shutcm.edu.cn) |
| 英文摘要 | Promoting tumor cell senescence arrests the cell cycle of tumor cells and activates the immune system to eliminate these senescent cells, thereby suppressing tumor growth. Nevertheless, PD-L1 positive senescent tumor cells resist immune clearance and possess the ability to secret various cytokines and inflammatory factors that stimulate the growth of tumor cells. Consequently, drugs capable of both triggering senescence in tumor cells and concurrently diminishing the expression of PD-L1 to counteract immune evasion are urgently needed. Here, a berberine derivative B68 is developed, which specifically induces tumor cell senescence by targeting BMI1. B68 also involves the degradation of PD-L1 by targeting CSN5, thereby disrupting the immunosuppressive PD-1/PD-L1 interaction and enabling rapid clearance of senescent tumor cells. This approach simultaneously inhibits tumor progression and activates T cell immunity, as evidenced by the robust antitumor response following B68-induced immunization of senescent cancer cells. Moreover, the synergistic effect of B68 with anti-CTLA4 therapy further enhances antitumor immunity, and its ability to induce senescence in cancer cells triggers a strong protective response by dendritic and CD8+ T cells. These findings provide a scientific basis for developing a new tumor treatment strategy based on senescence induction and lay the foundation for further preclinical research. |
| WOS关键词 | PD-1/PD-L1 BLOCKADE ; COLORECTAL-CANCER ; CELLS ; EXPRESSION ; DEUBIQUITINATION ; MICROENVIRONMENT |
| 资助项目 | National Natural Science Foundation of China ; National Key Research and Development Program of China[2022YFC3502000] ; Shanghai Municipal Science and Technology Major Project[ZD2021CY001] ; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[ZYYCXTDD-202004] ; Science and Technology Commission of Shanghai Municipality[20YF1458700] ; Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine[2023YZZ02] ; Shanghai Advanced Research Institute, Chinese Academy of Science, China ; [82374086] ; [82141203] ; [82104459] ; [22077131] ; [22277129] |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001382682200001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315172]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xu, Hanchen; Li, Bo; Zhang, Weidong; Liu, Sanhong |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Second Mil Med Univ, Sch Pharm, Dept Phytochem, Shanghai 200433, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Longhua Hosp, Inst Digest Dis, Shanghai 200032, Peoples R China 4.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 5.Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Plant Dev, Beijing 100193, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Chem Biol, Shanghai 201203, Peoples R China 7.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai Frontiers Sci Ctr TCM Chem Biol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hu, Hongmei,Wang, Qun,Yu, Dianping,et al. Berberine Derivative B68 Promotes Tumor Immune Clearance by Dual-Targeting BMI1 for Senescence Induction and CSN5 for PD-L1 Degradation[J]. ADVANCED SCIENCE,2024:21. |
| APA | Hu, Hongmei.,Wang, Qun.,Yu, Dianping.,Tao, Xiaoyu.,Guo, Mengmeng.,...&Liu, Sanhong.(2024).Berberine Derivative B68 Promotes Tumor Immune Clearance by Dual-Targeting BMI1 for Senescence Induction and CSN5 for PD-L1 Degradation.ADVANCED SCIENCE,21. |
| MLA | Hu, Hongmei,et al."Berberine Derivative B68 Promotes Tumor Immune Clearance by Dual-Targeting BMI1 for Senescence Induction and CSN5 for PD-L1 Degradation".ADVANCED SCIENCE (2024):21. |
入库方式： OAI收割
来源：上海药物研究所
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