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Role of GRP78 inhibiting artesunate-induced ferroptosis in KRAS mutant pancreatic cancer cells

Authors Wang K, Zhang Z, Wang M, Cao X, Qi J, Wang D, Gong A, Zhu H

Received 25 December 2018

Accepted for publication 15 May 2019

Published 2 July 2019 Volume 2019:13 Pages 2135—2144

DOI https://doi.org/10.2147/DDDT.S199459

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Sukesh Voruganti


Kang Wang,1,* Zhengyang Zhang,1,* Ming Wang,1 Xiongfeng Cao,1 Jianchen Qi,1 Dongqing Wang,1,2 Aihua Gong,3 Haitao Zhu1,2

1Central 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 work

Objective: 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

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