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Induction of ER stress protects gastric cancer cells against apoptosis induced by cisplatin and doxorubicin through activation of p38 MAPK
Authors:Ruo Feng  Wen Long Zhai  Hai Yan Yang  Hui Jin  Qin Xian Zhang
Affiliation:aDepartment of Histology and Embryology, Medical School of Zhengzhou University, Zhengzhou, Henan 450001, China;bDepartment of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China;cDepartment of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, Henan 450001, China
Abstract:We investigated the role of endoplasmic reticulum (ER) stress response and p38 MAPK pathways in the resistance of gastric cancer cells to chemotherapy. Pretreatment of the gastric cancer cells with the ER stress inducer drastically decreased the apoptotic rate induced by cisplatin or doxorubicin. Induction of ER stress also led to the activation of p38. Inhibition of p38 activity abrogated the effects of ER stress-induced resistance to apoptosis induced by cisplatin- and doxorubicin treatment. Thus, ER-stress response in gastric cancer cells causes resistance to cisplatin- and doxorubicin-induced apoptosis, and ER-stress induced chemo-resistance can be overcome by blocking p38 activity.
Keywords:p38 MAPK   ER stress   Gastric cancer   Apopsosis   Cisplatin   Doxorubicin
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