Induction of ER stress protects gastric cancer cells against apoptosis induced by cisplatin and doxorubicin through activation of p38 MAPK.

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.