GW4869 Can Inhibit Epithelial-Mesenchymal Transition and Extracellular HSP90α in Gefitinib-Sensitive NSCLC Cells
Xuan Wan,1,* Yuting Fang,2,* Jiangzhou Du,1 Shaoxi Cai,1 Hangming Dong1 1Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, People’s Republic of China; 2BSL-3...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2023-11-01
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| Series: | OncoTargets and Therapy |
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| Online Access: | https://www.dovepress.com/gw4869-can-inhibit-epithelial-mesenchymal-transition-and-extracellular-peer-reviewed-fulltext-article-OTT |
| _version_ | 1797634238790500352 |
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| author | Wan X Fang Y Du J Cai S Dong H |
| author_facet | Wan X Fang Y Du J Cai S Dong H |
| author_sort | Wan X |
| collection | DOAJ |
| description | Xuan Wan,1,* Yuting Fang,2,* Jiangzhou Du,1 Shaoxi Cai,1 Hangming Dong1 1Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, People’s Republic of China; 2BSL-3 Laboratory, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaoxi Cai; Hangming Dong, Email hxkc@smu.edu.cn; dhm@smu.edu.cnObjective: GW4869 is an exosomal inhibitor. It is necessary to delay the occurrence of gefitinib resistance during non-small-cell lung cancer (NSCLC) treatment. This study aimed to investigate the anti-tumor effects of GW4869 on epithelial-mesenchymal transition (EMT) and expression of extracellular heat shock protein 90α (eHSP90α) that contributes to acquired resisitance. Our study provides a new sight into the treatment of EGFR-mutated NSCLC.Materials and Methods: We performed western blotting to detect levels of EMT and eHSP90α. Wound healing and transwell assays were performed to evaluate the behavioral dynamics of EMT. A nude mouse model of HCC827 was established in vivo.Results: GW4869 inhibited the expression of eHSP90α, EMT, invasion and migration abilities of HCC827 and PC9. GW4869 enhanced sensitivity to gefitinib in BALB/c nude mice bearing tumors of HCC827.Conclusion: These studies suggest that GW4869 can inhibit EMT and extracellular HSP90α, providing new strategies for enhancing gefitinib sensitivity in NSCLC.Keywords: GW4869, EMT, gefitinib-sensitive NSCLC, eHSP90α |
| first_indexed | 2024-03-11T12:04:58Z |
| format | Article |
| id | doaj.art-a88fd65acf0148479868c97471b73aaa |
| institution | Directory Open Access Journal |
| issn | 1178-6930 |
| language | English |
| last_indexed | 2024-03-11T12:04:58Z |
| publishDate | 2023-11-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | OncoTargets and Therapy |
| spelling | doaj.art-a88fd65acf0148479868c97471b73aaa2023-11-07T17:06:36ZengDove Medical PressOncoTargets and Therapy1178-69302023-11-01Volume 1691392287989GW4869 Can Inhibit Epithelial-Mesenchymal Transition and Extracellular HSP90α in Gefitinib-Sensitive NSCLC CellsWan XFang YDu JCai SDong HXuan Wan,1,* Yuting Fang,2,* Jiangzhou Du,1 Shaoxi Cai,1 Hangming Dong1 1Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, People’s Republic of China; 2BSL-3 Laboratory, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaoxi Cai; Hangming Dong, Email hxkc@smu.edu.cn; dhm@smu.edu.cnObjective: GW4869 is an exosomal inhibitor. It is necessary to delay the occurrence of gefitinib resistance during non-small-cell lung cancer (NSCLC) treatment. This study aimed to investigate the anti-tumor effects of GW4869 on epithelial-mesenchymal transition (EMT) and expression of extracellular heat shock protein 90α (eHSP90α) that contributes to acquired resisitance. Our study provides a new sight into the treatment of EGFR-mutated NSCLC.Materials and Methods: We performed western blotting to detect levels of EMT and eHSP90α. Wound healing and transwell assays were performed to evaluate the behavioral dynamics of EMT. A nude mouse model of HCC827 was established in vivo.Results: GW4869 inhibited the expression of eHSP90α, EMT, invasion and migration abilities of HCC827 and PC9. GW4869 enhanced sensitivity to gefitinib in BALB/c nude mice bearing tumors of HCC827.Conclusion: These studies suggest that GW4869 can inhibit EMT and extracellular HSP90α, providing new strategies for enhancing gefitinib sensitivity in NSCLC.Keywords: GW4869, EMT, gefitinib-sensitive NSCLC, eHSP90αhttps://www.dovepress.com/gw4869-can-inhibit-epithelial-mesenchymal-transition-and-extracellular-peer-reviewed-fulltext-article-OTTgw4869emtgefitinib-sensitive nsclcehsp90α |
| spellingShingle | Wan X Fang Y Du J Cai S Dong H GW4869 Can Inhibit Epithelial-Mesenchymal Transition and Extracellular HSP90α in Gefitinib-Sensitive NSCLC Cells OncoTargets and Therapy gw4869 emt gefitinib-sensitive nsclc ehsp90α |
| title | GW4869 Can Inhibit Epithelial-Mesenchymal Transition and Extracellular HSP90α in Gefitinib-Sensitive NSCLC Cells |
| title_full | GW4869 Can Inhibit Epithelial-Mesenchymal Transition and Extracellular HSP90α in Gefitinib-Sensitive NSCLC Cells |
| title_fullStr | GW4869 Can Inhibit Epithelial-Mesenchymal Transition and Extracellular HSP90α in Gefitinib-Sensitive NSCLC Cells |
| title_full_unstemmed | GW4869 Can Inhibit Epithelial-Mesenchymal Transition and Extracellular HSP90α in Gefitinib-Sensitive NSCLC Cells |
| title_short | GW4869 Can Inhibit Epithelial-Mesenchymal Transition and Extracellular HSP90α in Gefitinib-Sensitive NSCLC Cells |
| title_sort | gw4869 can inhibit epithelial mesenchymal transition and extracellular hsp90 alpha in gefitinib sensitive nsclc cells |
| topic | gw4869 emt gefitinib-sensitive nsclc ehsp90α |
| url | https://www.dovepress.com/gw4869-can-inhibit-epithelial-mesenchymal-transition-and-extracellular-peer-reviewed-fulltext-article-OTT |
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