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

  • Drug Des Devel Ther. 2019 Jul 2;13:2135-2144. doi: 10.2147/DDDT.S199459.
Kang Wang   #  1 ,  Zhengyang Zhang   #  1 ,  Ming Wang  1 ,  Xiongfeng Cao  1 ,  Jianchen Qi  1 ,  Dongqing Wang  1  2 ,  Aihua Gong  3 ,  Haitao Zhu  1  2
Affiliations
  • 1. Central Laboratory of Medical Imaging, Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, People's Republic of China.
  • 2. Department of Radiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, People's Republic of China.
  • 3. School of Medicine, Jiangsu University, Zhenjiang 212013, People's Republic of China.
  • # Contributed equally.
PMID: 31456633 DOI: 10.2147/DDDT.S199459
Abstract

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
GRP78; artesunate; ferroptosis; pancreatic cancer.
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