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Anti-tumor Effects of Skp2 Inhibitor AAA-237 on NSCLC by Arresting Cell Cycle at G0/G1 Phase and Inducing Senescence.

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WOS体系：
Pubmed体系：

收录情况： ◇ SCIE

作者：
Liu Jinyi[1,2] * ; Zheng Xiangjin[1,2] ; Li Wan[1,2] ; Ren Liwen[1,2] ; Li Sha[1,2] ; Yang Yihui[1,2] ; Yang Hong[1,2] ; Ge Binbin[1,2] ; Du Guanhua[1,2] ; Shi Jianyou[3] ; Wang Jinhua[1,2,*1] ;
机构： [1]The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing 100050, China [2]Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China [3]Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial, People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China
出处：
DOI： 10.1016/j.phrs.2022.106259
ISSN：

关键词： AAA-237 Skp2 Cell cycle Apoptosis Senescence

摘要：
Lung cancer is by far the leading cause of cancer death worldwide, and 85% of patients are diagnosed with non-small cell lung cancer (NSCLC), which is still very difficult to treat. Skp2 functions as an oncogene that participates in processes of many cancers. Here, we report a novel Skp2 inhibitor AAA-237 that binds to Skp2 protein and inhibits the proliferation of the NSCLC cells. We further investigated the anti-NSCLC mechanism of AAA-237 and found that it arrested the cell cycle at the G0/G1 phase by targeting Skp2 to reduce the degradation of p21Cip1 and p27Kip1 or by transcriptionally activating FOXO1 to increase the mRNA expression of p21Cip1 and p27Kip1. More importantly, we found that treatment of a high concentration AAA-237 could induce apoptosis of NSCLC cells and treatment of a low AAA-237 concentration for a longer time could induce senescence of NSCLC cells. Similar results were found in nude mice xenografted with A549 cells. AAA-237 inhibited tumor growth by inducing apoptosis and senescence in a dose-dependent manner. Considering these results, we propose that AAA-237 could be a promising therapeutic drug for treating patients with NSCLC.Copyright © 2022. Published by Elsevier Ltd.

基金：
This research was funded by Beijing Natural Science Foundation (7212157), CAMS Innovation Fund for Medical Sciences (2021-I2M-1- 029), National Natural Science Foundation of China (81803584, 81703536), Technology Major Projects for “Major New Drugs Innovation and Development” (2018ZX09711001-005-025, 2018ZX09711001- 012), Natural Science Foundation of China (82073311), the Key Research and Development Projects in Chengdu (2020-YF05-00058- SN), the Key Research and Development Projects in Sichuan Province (2019YFS0514).
语种：
外文
被引次数：
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PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 医学
小类 | 1 区 药学
最新[2023]版：
大类 | 2 区 医学
小类 | 1 区 药学
JCR分区：
出版当年[2022]版：
Q1 PHARMACOLOGY & PHARMACY
最新[2023]版：
Q1 PHARMACOLOGY & PHARMACY

影响因子： 最新[2023版] 最新五年平均 出版当年[2022版] 出版当年五年平均 出版前一年[2021版] 出版后一年[2023版]

第一作者：
第一作者机构： [1]The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing 100050, China [2]Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China
通讯作者：
通讯机构： [1]The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing 100050, China [2]Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China [*1]The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing 100050, China.
推荐引用方式(GB/T 7714)：
Liu Jinyi,Zheng Xiangjin,Li Wan,et al.Anti-tumor Effects of Skp2 Inhibitor AAA-237 on NSCLC by Arresting Cell Cycle at G0/G1 Phase and Inducing Senescence.[J].PHARMACOLOGICAL RESEARCH.2022,181:doi:10.1016/j.phrs.2022.106259.
APA：
Liu Jinyi,Zheng Xiangjin,Li Wan,Ren Liwen,Li Sha...&Wang Jinhua.(2022).Anti-tumor Effects of Skp2 Inhibitor AAA-237 on NSCLC by Arresting Cell Cycle at G0/G1 Phase and Inducing Senescence..PHARMACOLOGICAL RESEARCH,181,
MLA：
Liu Jinyi,et al."Anti-tumor Effects of Skp2 Inhibitor AAA-237 on NSCLC by Arresting Cell Cycle at G0/G1 Phase and Inducing Senescence.".PHARMACOLOGICAL RESEARCH 181.(2022)

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