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

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...

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Detalles Bibliográficos
Autores principales: Wang, Kang, Zhang, Zhengyang, Wang, Ming, Cao, Xiongfeng, Qi, Jianchen, Wang, Dongqing, Gong, Aihua, Zhu, Haitao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Original Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620771/
https://www.ncbi.nlm.nih.gov/pubmed/31456633
http://dx.doi.org/10.2147/DDDT.S199459
Descripción
Sumario: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.

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