Regorafenib induces NOX5-mediated endoplasmic reticulum stress and potentiates the anti-tumor activity of cisplatin in non-small cell lung cancer cells

doi:10.1016/j.neo.2023.100897

科研成果详情

题名	Regorafenib induces NOX5-mediated endoplasmic reticulum stress and potentiates the anti-tumor activity of cisplatin in non-small cell lung cancer cells
作者	Sui, Hehuan1,2; Xiao, Sisi 1,2,3; Jiang, Suping1,2; Wu, Siyuan1,2; Lin, Haizhen 1,3; Cheng, Liyuan1,2; Ye, Lihua1,2; Zhao, Qi1,2; Yu, Yun1; Tao, Lu1; Kong, Feng-Ming3; Huang, Xiaoying 3; Cui, Ri1,2
发表日期	2023-05
发表期刊	Neoplasia (New York, N.Y.) 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	Cisplatin NOX5 NSCLC Reactive oxygen species Regorafenib
其他关键词	NADPH OXIDASES ; ROS ; APOPTOSIS ; ACTIVATION ; INHIBITOR ; 1ST-LINE ; THERAPY ; TARGETS
摘要	Lung cancer is one of the most commonly diagnosed cancers worldwide. Although cisplatin-based chemotherapy regimens serve a pivotal role in non-small cell lung cancer (NSCLC) treatment, drug resistance and serious side effects limited its further clinical application. Regorafenib, a small-molecule multi-kinase inhibitor, was demonstrated to have promising anti-tumor activity in various solid tumors. In the present study, we found that regorafenib markedly enhanced cisplatin-induced cytotoxicity in lung cancer cells by activating reactive oxygen species (ROS)-mediated endoplasmic reticulum stress (ER Stress), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. Regorafenib increased ROS generation by promoting NADPH oxidase 5 (NOX5) expression, and knocking down NOX5 attenuated ROS-mediated cytotoxicity of regorafenib in lung cancer cells. Additionally, mice xenograft model validated that synergistic anti-tumor effects of combined treatment with regorafenib and cisplatin. Our results suggested that combination therapy with regorafenib and cisplatin may serve as a potential therapeutic strategy for some NSCLC patients.
资助项目	National Natural Science Foundation of China [81672305]; Natural Science Foundation of Zhejiang Province [LZ22H160006]
出版者	ELSEVIER SCIENCE INC
ISSN	1476-5586
EISSN	1476-5586
卷号	39
DOI	10.1016/j.neo.2023.100897
页数	14
WOS类目	Oncology
WOS研究方向	Oncology
WOS记录号	WOS:000957807600001
收录类别	PUBMED ; SCIE ; SCOPUS
在线发表日期	2023-03
URL	查看原文
PubMed ID	36940556
SCOPUSEID	2-s2.0-85150380888
通讯作者地址	[Kong, Feng-Ming]The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China
Scopus学科分类	Cancer Research
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/174381
专题	附属第一医院药学院（分析测试中心）
通讯作者	Kong, Feng-Ming
作者单位	1.Cancer and Anticancer Drug Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 2.Wenzhou University-Wenzhou Medical University Collaborative Innovation Center of Biomedical,Wenzhou,325035,China; 3.The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China
第一作者单位	药学院（分析测试中心）; 温州医科大学
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Sui, Hehuan,Xiao, Sisi,Jiang, Suping,et al. Regorafenib induces NOX5-mediated endoplasmic reticulum stress and potentiates the anti-tumor activity of cisplatin in non-small cell lung cancer cells[J]. Neoplasia (New York, N.Y.),2023,39.
APA	Sui, Hehuan., Xiao, Sisi., Jiang, Suping., Wu, Siyuan., Lin, Haizhen., ... & Cui, Ri. (2023). Regorafenib induces NOX5-mediated endoplasmic reticulum stress and potentiates the anti-tumor activity of cisplatin in non-small cell lung cancer cells. Neoplasia (New York, N.Y.), 39.
MLA	Sui, Hehuan,et al."Regorafenib induces NOX5-mediated endoplasmic reticulum stress and potentiates the anti-tumor activity of cisplatin in non-small cell lung cancer cells".Neoplasia (New York, N.Y.) 39(2023).