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Imatinib inhibits the malignancy of hepatocellular carcinoma by suppressing autophagy

文献类型：期刊论文

作者Xiao, Meng-Chao2; Qian, Hui1; Huang, Chen-Kai3; Zheng, Bai-Nan1; Yan, Fang-Zhi1; Liu, Fang1; Zhang, Xin1; Chen, Shi-Jie4; Luo, Cheng4; Xie, Wei-Fen1,2
刊名EUROPEAN JOURNAL OF PHARMACOLOGY
出版日期2021-09-05
卷号906页码:8
ISSN号0014-2999
关键词Imatinib Autophagy Hepatocarcinoma Sorafenib Synergetic effect
DOI10.1016/j.ejphar.2021.174217
通讯作者Qian, Hui(qianhui1981@126.com.cn) ; Xie, Wei-Fen(weifenxie@medmail.com.cn)
英文摘要Hepatocellular carcinoma (HCC) is one of the most common cancers and is associated with high morbidity and mortality rates. Recent research indicated that imatinib, a selective tyrosine kinase inhibitor, suppressed the growth of hepatocellular carcinoma. However, the effect of imatinib on HCC and its mechanism remain under investigated. In this study, we demonstrated that imatinib inhibited the proliferation, migration and invasion of HCC cells in vitro and exerted antitumour effects on HCC xenografts in mice in vivo. Imatinib treatment decreased the phosphorylation of AKT and increased the levels of both p62 (protein sequestosome 1) and LC3 (microtubule-associated protein 1A/1B-light chain 3) in HCC cells and HCC xenografts. Scanning confocal microscopy analysis with a mRFP-GFP-LC3 reporter and transmission electron microscopy analysis revealed that imatinib suppressed the autophagic flux by obstructing the formation of autolysosomes. Moreover, imatinib reversed the autophagy induced by sorafenib, and combined treatment with imatinib and sorafenib exerted a synergetic effect in HCC cells compared with monotherapy. Our collective data suggested that imatinib may target HCC by acting as an inhibitor of both tyrosine kinase and autophagy; here, we propose that imatinib could be a promising therapeutic agent for HCC in the clinic.
WOS关键词TARGETING AUTOPHAGY ; SORAFENIB RESISTANCE ; CELL-DEATH ; HYDROXYCHLOROQUINE ; DEGRADATION ; MECHANISMS ; LEUKEMIA ; CANCER ; TUMOR
资助项目National Natural Science Foundation of China[82030021] ; National Natural Science Foundation of China[82072641] ; Shanghai Science and Technology Foundation[201740145]
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者ELSEVIER
WOS记录号WOS:000691549900004
源URL[http://119.78.100.183/handle/2S10ELR8/297682]  
专题新药研究国家重点实验室
通讯作者Qian, Hui; Xie, Wei-Fen
作者单位1.Navy Med Univ, Dept Gastroenterol, Changzheng Hosp, 415 Fengyang Rd, Shanghai 200003, Peoples R China
2.Tongji Univ, Sch Med, Shanghai 200120, Peoples R China
3.Nanchang Univ, Dept Gastroenterol, Affiliated Hosp 1, Nanchang, Jiangxi, Peoples R China
4.Chinese Acad Sci, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, State Key Lab Drug Res,Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Xiao, Meng-Chao,Qian, Hui,Huang, Chen-Kai,et al. Imatinib inhibits the malignancy of hepatocellular carcinoma by suppressing autophagy[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2021,906:8.
APA Xiao, Meng-Chao.,Qian, Hui.,Huang, Chen-Kai.,Zheng, Bai-Nan.,Yan, Fang-Zhi.,...&Xie, Wei-Fen.(2021).Imatinib inhibits the malignancy of hepatocellular carcinoma by suppressing autophagy.EUROPEAN JOURNAL OF PHARMACOLOGY,906,8.
MLA Xiao, Meng-Chao,et al."Imatinib inhibits the malignancy of hepatocellular carcinoma by suppressing autophagy".EUROPEAN JOURNAL OF PHARMACOLOGY 906(2021):8.

入库方式： OAI收割

来源：上海药物研究所

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