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β-Elemene enhances erlotinib sensitivity through induction of ferroptosis by upregulating lncRNA H19 in EGFR-mutant non-small cell lung cancer

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机构： [1]State Key Laboratory of Quality Research in Chinese Medicine and Faculty of Chinese Medicine, Macau University of Science and Technology, 999078, Macao Special Administrative Region of China [2]Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 519000, Guangdong, China [3]The First Hospital, Hunan University of Chinese Medicine, Changsha 410007, Hunan, China [4]College of Pharmacy, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China [5]Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 310015, Zhejiang, China [6]Cancer Center, Faculty of Health Science, University of Macau, 999078, Macao Special Administrative Region of China [7]MOE Frontiers Science Center for Precision Oncology, University of Macau, 999078, Macao Special Administrative Region of China [8]Zhuhai MUST Science and Technology Research Institute, Zhuhai 51900, Guangdong, China [9]Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, China

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关键词： β-elemene Erlotinib Ferroptosis LncRNA H19 NSCLC

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Nearly half of all Asian non-small cell lung cancer (NSCLC) patients harbour epidermal growth factor receptor (EGFR) mutations, and first-generation EGFR tyrosine kinase inhibitors (TKIs) are one of the first-line treatments that have improved the outcomes of these patients. Unfortunately, 20% of these patients can not benefit from the treatment. The basis of this primary resistance is poorly understood. Therefore, overcoming EGFR-TKI primary resistance and maintaining the efficacy of TKIs has become a key issue. β-Elemene, a sesquiterpene compound extracted from Curcuma aromatica Salisb. (wenyujing), has shown potent antitumor effects. In this research, we found that β-elemene combined with erlotinib enhanced the cytotoxicity of erlotinib to primary EGFR-TKI-resistant NSCLC cells with EGFR mutations and that ferroptosis was involved in the antitumor effect of the combination treatment. We found that lncRNA H19 was significantly downregulated in primary EGFR-TKI-resistant NSCLC cell lines and was upregulated by the combination treatment. Overexpression or knockdown of H19 conferred sensitivity or resistance to erlotinib, respectively, in both in vitro and in vivo studies. The high level of H19 enhanced the cytotoxicity of erlotinib by inducing ferroptosis. In conclusion, our data showed that β-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

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出版当年[2022]版：

大类 | 1 区

医学

小类 | 1 区药学

最新[2025]版：

大类 | 2 区

医学

小类 | 1 区药学

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出版当年[2021]版：

Q1 PHARMACOLOGY & PHARMACY

最新[2023]版：

Q1 PHARMACOLOGY & PHARMACY

影响因子： 9.1 最新[2023版] 9 最新五年平均 10.334 出版当年[2021版] 9.105 出版当年五年平均 7.658 出版前一年[2020版] 9.3 出版后一年[2022版]

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第一作者机构： [1]State Key Laboratory of Quality Research in Chinese Medicine and Faculty of Chinese Medicine, Macau University of Science and Technology, 999078, Macao Special Administrative Region of China

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通讯机构： [1]State Key Laboratory of Quality Research in Chinese Medicine and Faculty of Chinese Medicine, Macau University of Science and Technology, 999078, Macao Special Administrative Region of China [6]Cancer Center, Faculty of Health Science, University of Macau, 999078, Macao Special Administrative Region of China [7]MOE Frontiers Science Center for Precision Oncology, University of Macau, 999078, Macao Special Administrative Region of China [8]Zhuhai MUST Science and Technology Research Institute, Zhuhai 51900, Guangdong, China [9]Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, School of Environmental Science and Engineering, Institute of Environmental Health and Pollution Control, Guangdong University of Technology, Guangzhou 510006, China [*1]Cancer Center, Faculty of Health Science, University of Macau, 999078, Macao Special Administrative Region of China. [*2]State Key Laboratory of Quality Research in Chinese Medicine and Faculty of Chinese Medicine, Macau University of Science and Technology, 999078, Macao Special Administrative Region of China.

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β-Elemene enhances erlotinib sensitivity through induction of ferroptosis by upregulating lncRNA H19 in EGFR-mutant non-small cell lung cancer