title: Induction of ER stress protects gastric cancer cells against apoptosis induced by cisplatin and doxorubicin through activation of p38 MAPK.
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.
authors.affiliation: Department of Histology and Embryology, Medical School of Zhengzhou University, Zhengzhou, Henan 450001, China.
authors.forename: Ruo
authors.initials: R
authors.lastname: Feng
authors.forename: Wen Long
authors.initials: WL
authors.lastname: Zhai
authors.forename: Hai Yan
authors.initials: HY
authors.lastname: Yang
authors.forename: Hui
authors.initials: H
authors.lastname: Jin
authors.forename: Qin Xian
authors.initials: QX
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013312:Stress, Physiological; D056811:Unfolded Protein Response
chemical_list: D000970:Antineoplastic Agents; D011518:Proto-Oncogene Proteins; D004317:Doxorubicin; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human; D002945:Cisplatin