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Chloroquine enhances the efficacy of chemotherapy drugs against acute myeloid leukemia by inactivating the autophagy pathway

文献类型：期刊论文

作者Wang, Han-lin1,7,8; Li, Jia-nan2; Kan, Wei-juan8; Xu, Gao-ya2; Luo, Guang-hao1,3,8; Song, Ning8; Wu, Wen-biao1,3,8; Feng, Bo4,8; Fu, Jing-feng1,8; Tu, Yu-tong1,8
刊名ACTA PHARMACOLOGICA SINICA
出版日期2023-06-14
页码11
ISSN号1671-4083
关键词acute myeloid leukemia cytarabine daunorubicin idarubicin drug resistant multi-omics autophagy chloroquine phosphate
DOI10.1038/s41401-023-01112-8
通讯作者Zhou, Yu-bo(ybzhou@simm.ac.cn) ; Wei, Gang(weigang@shmu.edu.cn) ; Li, Jia(jli@simm.ac.cn)
英文摘要Current therapy for acute myeloid leukemia (AML) is largely hindered by the development of drug resistance of commonly used chemotherapy drugs, including cytarabine, daunorubicin, and idarubicin. In this study, we investigated the molecular mechanisms underlying the chemotherapy drug resistance and potential strategy to improve the efficacy of these drugs against AML. By analyzing data from ex vivo drug-response and multi-omics profiling public data for AML, we identified autophagy activation as a potential target in chemotherapy-resistant patients. In THP-1 and MV-4-11 cell lines, knockdown of autophagy-regulated genes ATG5 or MAP1LC3B significantly enhanced AML cell sensitivity to the chemotherapy drugs cytarabine, daunorubicin, and idarubicin. In silico screening, we found that chloroquine phosphate mimicked autophagy inactivation. We showed that chloroquine phosphate dose-dependently down-regulated the autophagy pathway in MV-4-11 cells. Furthermore, chloroquine phosphate exerted a synergistic antitumor effect with the chemotherapy drugs in vitro and in vivo. These results highlight autophagy activation as a drug resistance mechanism and the combination therapy of chloroquine phosphate and chemotherapy drugs can enhance anti-AML efficacy.
WOS关键词DEOXYCYTIDINE KINASE ; CISPLATIN RESISTANCE ; CONNECTIVITY MAP ; CANCER ; INHIBITION ; CELLS ; SENSITIVITY ; ACTIVATION ; MECHANISMS ; EXPRESSION
资助项目National Natural Science Foundation of China[81821005] ; Guangdong High-level New RD Institute[2019B090904008] ; Guangdong High-level Innovative Research Institute[2021B0909050003] ; Science and Technology Commission of Shanghai Municipality[18431907100] ; Science and Technology Commission of Shanghai Municipality[19430750100]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
出版者NATURE PUBL GROUP
WOS记录号WOS:001005804200001
源URL[http://119.78.100.183/handle/2S10ELR8/306272]  
专题新药研究国家重点实验室
通讯作者Zhou, Yu-bo; Wei, Gang; Li, Jia
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310000, Peoples R China
4.Shenyang Pharmaceut Univ, Sch Life Sci & Biopharmaceut, Shenyang 110016, Peoples R China
5.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
6.Jiangnan Univ, Sch Pharmaceut Sci, Wuxi 214122, Peoples R China
7.Fudan Univ, Sch Pharm, Shanghai 210023, Peoples R China
8.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Han-lin,Li, Jia-nan,Kan, Wei-juan,et al. Chloroquine enhances the efficacy of chemotherapy drugs against acute myeloid leukemia by inactivating the autophagy pathway[J]. ACTA PHARMACOLOGICA SINICA,2023:11.
APA Wang, Han-lin.,Li, Jia-nan.,Kan, Wei-juan.,Xu, Gao-ya.,Luo, Guang-hao.,...&Li, Jia.(2023).Chloroquine enhances the efficacy of chemotherapy drugs against acute myeloid leukemia by inactivating the autophagy pathway.ACTA PHARMACOLOGICA SINICA,11.
MLA Wang, Han-lin,et al."Chloroquine enhances the efficacy of chemotherapy drugs against acute myeloid leukemia by inactivating the autophagy pathway".ACTA PHARMACOLOGICA SINICA (2023):11.

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来源：上海药物研究所

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