Role of GRP78 inhibiting artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cells
Kang Wang,1,* Zhengyang Zhang,1,* Ming Wang,1 Xiongfeng Cao,1 Jianchen Qi,1 Dongqing Wang,1,2 Aihua Gong,3 Haitao Zhu1,21Central Laboratory of Medical Imaging, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, People’s Republic of China; 2Department o...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-07-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://www.dovepress.com/role-of-grp78-inhibiting-artesunate-induced-ferroptosis-in-kras-mutant-peer-reviewed-article-DDDT |
| _version_ | 1819174280702722048 |
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| author | Wang K Zhang Z Wang M Cao X Qi J Wang D Gong A Zhu H |
| author_facet | Wang K Zhang Z Wang M Cao X Qi J Wang D Gong A Zhu H |
| author_sort | Wang K |
| collection | DOAJ |
| description | Kang Wang,1,* Zhengyang Zhang,1,* Ming Wang,1 Xiongfeng Cao,1 Jianchen Qi,1 Dongqing Wang,1,2 Aihua Gong,3 Haitao Zhu1,21Central Laboratory of Medical Imaging, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, People’s Republic of China; 2Department of Radiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, People’s Republic of China; 3School of Medicine, Jiangsu University, Zhenjiang 212013, People’s Republic of China*These authors contributed equally to this workObjective: To investigate the exact role of GRP78 in artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cells.Methods: Artesunate-induced KRAS mutant human pancreatic cancer cells (AsPC-1 and PaTU8988) ferroptosis was confirmed by fluorescent staining experiments and CCK8. Western blot and short-hairpin RNA-based knockdown assays were conducted to detect GRP78 activity and its role in artesunate-induced ferroptosis.Results: Artesunate induced AsPC-1 and PaTU8988 cell death in ferroptosis manner, rather than necrosis or apoptosis. In addition, artesunate increased the mRNA and protein levels of GRP78 in a concentration-dependent manner in AsPC-1 and PaTU8988 cells. Knockdown GRP78 enhanced artesunate-induced ferroptosis of pancreatic cancer cells in vitro and in vivo.Conclusion: Combining artesunate with GRP78 inhibition may be a novel maneuver for effective killing of KRAS mutant pancreatic ductal adenocarcinoma cells.Keywords: ferroptosis, GRP78, artesunate, pancreatic cancer |
| first_indexed | 2024-12-22T20:36:28Z |
| format | Article |
| id | doaj.art-dcbf8b4ff55c460dac6f9c35055b82df |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-22T20:36:28Z |
| publishDate | 2019-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-dcbf8b4ff55c460dac6f9c35055b82df2022-12-21T18:13:27ZengDove Medical PressDrug Design, Development and Therapy1177-88812019-07-01Volume 132135214446766Role of GRP78 inhibiting artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cellsWang KZhang ZWang MCao XQi JWang DGong AZhu HKang Wang,1,* Zhengyang Zhang,1,* Ming Wang,1 Xiongfeng Cao,1 Jianchen Qi,1 Dongqing Wang,1,2 Aihua Gong,3 Haitao Zhu1,21Central Laboratory of Medical Imaging, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, People’s Republic of China; 2Department of Radiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, People’s Republic of China; 3School of Medicine, Jiangsu University, Zhenjiang 212013, People’s Republic of China*These authors contributed equally to this workObjective: To investigate the exact role of GRP78 in artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cells.Methods: Artesunate-induced KRAS mutant human pancreatic cancer cells (AsPC-1 and PaTU8988) ferroptosis was confirmed by fluorescent staining experiments and CCK8. Western blot and short-hairpin RNA-based knockdown assays were conducted to detect GRP78 activity and its role in artesunate-induced ferroptosis.Results: Artesunate induced AsPC-1 and PaTU8988 cell death in ferroptosis manner, rather than necrosis or apoptosis. In addition, artesunate increased the mRNA and protein levels of GRP78 in a concentration-dependent manner in AsPC-1 and PaTU8988 cells. Knockdown GRP78 enhanced artesunate-induced ferroptosis of pancreatic cancer cells in vitro and in vivo.Conclusion: Combining artesunate with GRP78 inhibition may be a novel maneuver for effective killing of KRAS mutant pancreatic ductal adenocarcinoma cells.Keywords: ferroptosis, GRP78, artesunate, pancreatic cancerhttps://www.dovepress.com/role-of-grp78-inhibiting-artesunate-induced-ferroptosis-in-kras-mutant-peer-reviewed-article-DDDTFerroptosisGRP78Artesunatepancreatic cancer |
| spellingShingle | Wang K Zhang Z Wang M Cao X Qi J Wang D Gong A Zhu H Role of GRP78 inhibiting artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cells Drug Design, Development and Therapy Ferroptosis GRP78 Artesunate pancreatic cancer |
| title | Role of GRP78 inhibiting artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cells |
| title_full | Role of GRP78 inhibiting artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cells |
| title_fullStr | Role of GRP78 inhibiting artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cells |
| title_full_unstemmed | Role of GRP78 inhibiting artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cells |
| title_short | Role of GRP78 inhibiting artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cells |
| title_sort | role of grp78 inhibiting artesunate induced ferroptosis in kras mutant pancreatic cancer cells |
| topic | Ferroptosis GRP78 Artesunate pancreatic cancer |
| url | https://www.dovepress.com/role-of-grp78-inhibiting-artesunate-induced-ferroptosis-in-kras-mutant-peer-reviewed-article-DDDT |
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