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

TitleRegorafenib induces NOX5-mediated endoplasmic reticulum stress and potentiates the anti-tumor activity of cisplatin in non-small cell lung cancer cells
Authors
KeywordsCisplatin
NOX5
NSCLC
Reactive oxygen species
Regorafenib
Issue Date1-May-2023
PublisherElsevier
Citation
Neoplasia, 2023, v. 39 How to Cite?
Abstract

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.

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Persistent Identifierhttp://hdl.handle.net/10722/343933
ISSN
2014 Impact Factor: 4.252
2023 SCImago Journal Rankings: 1.887

 

DC FieldValueLanguage
dc.contributor.authorSui, Hehuan-
dc.contributor.authorXiao, Sisi-
dc.contributor.authorJiang, Suping-
dc.contributor.authorWu, Siyuan-
dc.contributor.authorLin, Haizhen-
dc.contributor.authorCheng, Liyuan-
dc.contributor.authorYe, Lihua-
dc.contributor.authorZhao, Qi-
dc.contributor.authorYu, Yun-
dc.contributor.authorTao, Lu-
dc.contributor.authorKong, Feng-ming-
dc.contributor.authorHuang, Xiaoying-
dc.contributor.authorCui, Ri-
dc.date.accessioned2024-06-18T03:42:55Z-
dc.date.available2024-06-18T03:42:55Z-
dc.date.issued2023-05-01-
dc.identifier.citationNeoplasia, 2023, v. 39-
dc.identifier.issn1522-8002-
dc.identifier.urihttp://hdl.handle.net/10722/343933-
dc.description.abstract<p>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.</p><ul>​​​​​​​</ul>-
dc.languageeng-
dc.publisherElsevier-
dc.relation.ispartofNeoplasia-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCisplatin-
dc.subjectNOX5-
dc.subjectNSCLC-
dc.subjectReactive oxygen species-
dc.subjectRegorafenib-
dc.titleRegorafenib induces NOX5-mediated endoplasmic reticulum stress and potentiates the anti-tumor activity of cisplatin in non-small cell lung cancer cells-
dc.typeArticle-
dc.identifier.doi10.1016/j.neo.2023.100897-
dc.identifier.scopuseid_2-s2.0-85150380888-
dc.identifier.volume39-
dc.identifier.eissn1476-5586-
dc.identifier.issnl1476-5586-

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